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Review

Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/β-Catenin Signaling Pathway in Tumor Progression

by
Xinbing Yang
1,
Yajing Du
1,
Lulu Luo
1,
Xinru Xu
1,
Shizheng Xiong
2,
Xueni Yang
2,
Li Guo
2,* and
Tingming Liang
1,*
1
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China
2
Department of Bioinformatics, Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(18), 13909; https://doi.org/10.3390/ijms241813909
Submission received: 31 July 2023 / Revised: 4 September 2023 / Accepted: 8 September 2023 / Published: 10 September 2023
(This article belongs to the Special Issue Roles of Non-coding RNAs in Diseases)
Browse Figure
Versions Notes

Abstract

Dysregulated expression of specific non-coding RNAs (ncRNAs) has been strongly linked to tumorigenesis, cancer progression, and therapeutic resistance. These ncRNAs can act as either oncogenes or tumor suppressors, thereby serving as valuable diagnostic and prognostic markers. Numerous studies have implicated the participation of ncRNAs in the regulation of diverse signaling pathways, including the pivotal Wnt/β-catenin signaling pathway that is widely acknowledged for its pivotal role in embryogenesis, cellular proliferation, and tumor biology control. Recent emerging evidence has shed light on the capacity of ncRNAs to interact with key components of the Wnt/β-catenin signaling pathway, thereby modulating the expression of Wnt target genes in cancer cells. Notably, the activity of this pathway can reciprocally influence the expression levels of ncRNAs. However, comprehensive analysis investigating the specific ncRNAs associated with the Wnt/β-catenin signaling pathway and their intricate interactions in cancer remains elusive. Based on these noteworthy findings, this review aims to unravel the intricate associations between ncRNAs and the Wnt/β-catenin signaling pathway during cancer initiation, progression, and their potential implications for therapeutic interventions. Additionally, we provide a comprehensive overview of the characteristics of ncRNAs and the Wnt/β-catenin signaling pathway, accompanied by a thorough discussion of their functional roles in tumor biology. Targeting ncRNAs and molecules associated with the Wnt/β-catenin signaling pathway may emerge as a promising and effective therapeutic strategy in future cancer treatments.

1. Background

Cancer is a significant global public health issue, with a continuously increasing incidence and mortality rate. It imposes a tremendous burden on both individuals and societies worldwide [1]. The development of cancer is a complex process involving genetic and epigenetic alterations [2,3,4]. Changes in the regulation of certain molecules in cancer-generating genes and signaling pathways may be important information for cancer diagnosis and treatment [5,6]. Moreover, research on this information may further advance the field of cancer diagnostics and targeted therapies. The Wnt/β-catenin signaling pathway predominantly regulates essential biological functions, such as early embryo development, tissue regeneration, cell proliferation, differentiation, migration, and apoptosis [7,8]. It plays a vital role in tumor initiation and treatment. The previous literature has reported that the Wnt/β-catenin pathway is a key driving factor in cancer development and a hot target in current cancer therapeutics [9,10,11,12]. Disruption of this signaling pathway is closely associated with the occurrence and progression of various types of cancer [13,14,15].
Recent studies have shown that non-coding RNAs (ncRNAs), as well as Wnt/β-catenin signal pathways, play an active role in the development and progression of cancer [16]. ncRNAs are a unique class of transcripts that lack protein-coding capacity [17]. Currently identified ncRNAs primarily fall into three categories: microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) [18,19]. Previously considered as “junk DNA”, ncRNAs have been increasingly recognized for their central role in gene regulation and their significant impact on tumor pathways under physiological and pathological conditions [19,20,21,22]. The activation and silencing of the Wnt/β-catenin signaling pathway, as well as abnormal expression of ncRNAs, are closely linked to cancer development. Many existing experimental studies have demonstrated that aberrant expression of ncRNAs can affect behaviors, such as cancer migration and invasion, by regulating the activation and silencing of this Wnt/β-catenin signaling pathway.
This review aims to summarize the impact of abnormal expression of ncRNAs related to the Wnt/β-catenin signaling pathway on cancer initiation and development. It intends to elucidate the regulatory relationship between ncRNAs and the Wnt/β-catenin pathway. Additionally, it aims to provide an overview of the current application value and potential of ncRNAs in cancer diagnosis and treatment, thereby offering further insights for future research on the role of ncRNAs in tumor initiation and therapeutics. The ncRNAs data were retrieved through a comprehensive search on NCBI (PubMed), employing specific keywords, such as “ncRNA”, “Wnt/β-catenin”, and various types of cancer like “breast”, “lung”, “colorectal”, “prostate”, and “gastric cancer.” The search results were further filtered to encompass publications between the years 2019 and 2023.

2. Introduction to the Wnt Signaling Pathway and the Involvement of ncRNAs in Cancer

ncRNAs, a special class of RNA transcripts, do not encode proteins but exhibit high specificity and stability, making them crucial for assessing the occurrence and progression of cancer [23,24]. Based on their functions, ncRNAs are typically categorized into housekeeping RNAs and regulatory RNAs [25]. Regulatory RNAs mainly include miRNAs, lncRNAs, and circRNAs [23,24,25,26]. miRNAs are extensively studied small non-coding RNAs (sncRNAs) in eukaryotes and consist of approximately 22 nucleotides (nt) in length [27]. miRNAs recognize target mRNAs through complementary base pairing, leading to the degradation of the targeted mRNA or the silencing of mRNA translation by the RNA-induced silencing complex (RISC), thereby inhibiting gene expression [27,28]. A single miRNA can regulate multiple different genes, and multiple miRNAs can jointly regulate a single gene. This intricate regulatory network is increasingly associated with the abnormal expression of miRNAs and the progression of various cancers [29,30].
Both lncRNAs and circRNAs are over 200 nt in length; can be transcribed from the exon, the intron, the intergenic region of the gene, and the 5/3-untranslated region; and fold into complex secondary structures that facilitate their interactions with DNA, RNA, and proteins [31,32,33,34,35]. Through various mechanisms, lncRNAs and circRNAs regulate gene expression. They can serve as competitive endogenous RNAs (ceRNAs) that act as decoys or sponges, competitively sequestering miRNAs and forming intricate lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA networks, thereby regulating the expression levels of downstream target genes. Additionally, they can act as scaffolds to modulate protein–protein interactions and downstream signaling pathways. Recent studies have also identified the critical role of lncRNA-mediated regulation of Wnt/β-catenin signaling in epithelial–mesenchymal transition (EMT) processes in human tumors [36]. Over the past decade or so, ncRNAs have changed their role from “junk” transcription products to functional regulatory molecules that mediate cellular processes and participate in various cellular functions in many cancers through various signaling pathways, including Wnt/β-catenin [37]. For example, LINC01133 acts as a ceRNA for miR-106a-3p, regulating APC expression and the Wnt/β-catenin pathway, thereby inhibiting the progression and metastasis of gastric cancer cells [38]. Downregulation of miR-125b and inhibition of Wnt/β-catenin signaling inhibit proliferation and migration in TNBC [39]. Additionally, circ_0082182 activation of the Wnt/β-catenin pathway by absorption of miR-411 and miR-1205 through sponge action promotes malignant progression of colorectal cancer cells [40].
The Wnt signaling pathway is an important pathway widely present in multicellular organisms. It plays a crucial role in biological development, tissue regeneration, and various diseases, particularly in the occurrence and progression of cancer [41,42,43]. Furthermore, the composition of this pathway is highly conserved throughout evolution. The core genes of this pathway include Wnt, frizzled receptors, disheveled (DSH), GSK-3β, AXIN and β-catenin, among others. Among them, the Wnt protein is a critical entity that guides the signal transduction in this pathway.
Upon activation of the Wnt signaling pathway, downstream signaling requires the further activation of DSH. DSH consists of three distinct structural domains: the amino-terminal DIX domain, the central PDZ domain, and the carboxy-terminal DEP domain. These three domains of DSH play a crucial switch-like role in the Wnt signaling pathway [44] and determine the branching of the Wnt signal into different downstream pathways. The branching results in the formation of different Wnt pathways, including the Wnt/β-catenin or classical Wnt signaling pathway, the Wnt/Ca2+ signaling pathway, and the planar cell polarity (PCP) pathway [45,46]. Each of the three branches has different functions and participates in the regulation of various physiological activities.
Currently, research on the Wnt pathway primarily focuses on the Wnt/β-catenin signaling pathway branch. This pathway can determine cell fate, cell proliferation, cell survival, and intercellular interactions [47]. Dysregulation of this pathway is associated with the development of various malignancies [15,48,49,50,51,52,53]. For example, upregulation of the Wnt/β-catenin signaling pathway induced by gene mutations or abnormal activation of Wnt receptors can lead to the carcinogenesis of several tissues, such as the liver, lung, pancreas, and colon [54,55,56,57,58,59].
The interplay between ncRNAs in regulating the Wnt/β-catenin signaling pathway is depicted in Figure 1. Wnt serves as the major regulatory factor for β-catenin. β-catenin is a member of a family consisting of 19 cadherin proteins and can regulate both dependent and independent signaling pathways of β-catenin [60]. The distinct feature of the Wnt/β-catenin signaling pathway is the formation of a complex involving Wnt, its core receptor complex, and members of the frizzled (FZD) protein family, which regulates the degradation and protection of β-catenin during signal transduction [61]. In the presence of Wnt protein ligands, Wnt binds to FZD receptors and co-receptor LRP to form a complex. The LRP receptor is then phosphorylated by CK1α and GSK3β, which recruit DSH at the cell membrane, where they aggregate and activate. Once activated, they inhibit the activity of the degradation complex, allowing unphosphorylated β-catenin to translocate to the nucleus and accumulate. It then binds to LEF-1/TCF4 and other co-regulatory factors in a tissue-specific manner to promote the transcription of target genes. This activation of downstream target genes drives cell-cycle progression or generates abnormal proteins, leading to cellular carcinogenesis [62]. In the absence of stable Wnt ligands, β-catenin in the cytoplasm is recruited to a complex involving adenomatous polyposis coli (APC) and Axin, promoting the phosphorylation of β-catenin by casein kinase 1α (CK1α) and glycogen synthase kinase 3β (GSK3β). Phosphorylation of specific sites leads to the binding of E3 ubiquitin protein ligase subunits, targeting β-catenin for proteasomal degradation, thus maintaining low levels of β-catenin in the cytoplasm [55]. Without nuclear translocation of β-catenin, in the absence of β-catenin, inhibitory complexes containing T-cell factor/lymphoid enhancer factor (TCF/LEF) and transducin-like enhancer protein (TLE/Groucho) recruit histone deacetylase (HDAC) to suppress target gene transcription, leading to the inhibition of downstream target genes [63,64,65,66]. In more than half of cancer cases, such as colorectal cancer, breast cancer, liver cancer, and melanoma, β-catenin accumulates in the nucleus or cytoplasm [67,68,69,70].
An increasing body of research has demonstrated the significant regulatory roles of ncRNAs in the occurrence and progression of various cancers through the modulation of the Wnt signaling pathway. The Wnt pathway is known to play crucial roles in cell differentiation, proliferation, and self-renewal in a variety of cells. Disturbances in the Wnt pathway have been closely associated with the development and progression of several cancers, including liver cancer, colon cancer, breast cancer, and prostate cancer. As a class of RNA molecules that do not encode proteins, ncRNAs have garnered extensive attention regarding their mechanisms and regulatory modes in cancer. The specific mechanisms of ncRNAs vary among different types of cancer. For example, in bladder urothelial carcinoma, miRNA-139-3p inhibits malignant progression by targeting KIF18B and inactivating the Wnt/β-catenin pathway [71]. In contrast, in liver cancer, miR-342 promotes cell proliferation and apoptosis in hepatocellular carcinoma through the Wnt/β-catenin signaling pathway [72]. CircRNAs and lncRNAs have also received widespread attention for their role in cancer development. For instance, the expression levels of the lncRNA HOTAIR are elevated in various cancers. It can promote the proliferation and invasion of renal cell carcinoma by regulating the Wnt/β-catenin pathway and influencing cisplatin resistance [73]. Additionally, other Wnt signaling-pathway-related genes, such as AXIN2, DKK, and SFRP, as well as various classes of ncRNAs that regulate them, are closely associated with the occurrence and progression of multiple cancers. In addition to the well-known factors of the Wnt/β-catenin signaling pathway, certain genes seemingly unrelated to this pathway can also become major targets of ncRNA regulation. ncRNAs can modulate the expression of these genes through various mechanisms such as gene substrate competition, transcriptional regulation, and signal transduction regulation. This ultimately leads to direct or indirect effects on the β-catenin pathway, even if the ncRNAs themselves are not members of the pathway. The recent literature has reported that CREPT [74], as a co-activator, can enhance the transcriptional activity of the β-catenin–TCF4 complex stimulated by Wnt signaling. Additionally, miR-449b-5p has been identified as a regulator of Wnt/β-catenin signaling by targeting CREPT [75]. These findings suggest that the regulatory network of the Wnt/β-catenin pathway is more complex than previously thought. It highlights the importance of considering the involvement of seemingly unrelated genes and ncRNAs in the modulation of this signaling pathway. Further understanding the mechanisms through which ncRNAs regulate non-canonical target genes provides valuable insights into the intricate regulation of the cell and the transmission of Wnt/β-catenin signaling. The identified roles of CREPT and miR-449b-5p in this context open up new avenues for investigating the potential therapeutic implications of targeting ncRNA-mediated regulation in Wnt/β-catenin signaling.
Despite the need for further research to gain a deeper understanding of the mechanisms by which ncRNAs contribute to cancer, the study of ncRNAs and their regulation of the Wnt pathway hold great significance for cancer diagnosis, treatment, and the development of personalized medicine in the future.

3. The Roles and Mechanisms of ncRNAs Involved in the Wnt/β-Catenin Signaling Pathway in Tumors

In the past few years, ceRNA has been detected in Wnt/β-Catenin signaling-pathway-related cancers, exhibiting increasingly important regulatory roles (Table 1), particularly in breast cancer, lung cancer, colorectal cancer, prostate cancer, and gastric cancer.

3.1. The Impact of the Interplay between ncRNAs and the Wnt/β-Catenin Signaling Pathway on Breast Cancer

Breast cancer (BC), as a common disease threatening women’s health, has been receiving much attention in terms of its treatment and prognosis [1]. The Wnt/β-catenin signaling pathway plays a key regulatory role in the initiation and progression of BC. In recent years, more and more studies have revealed that this pathway is widely regulated by ncRNA. These ncRNAs assume important functions in BC, including regulation of Wnt/β-catenin activation, regulation of the expression of related genes, and adjustment of biological behaviors, such as cell proliferation, invasion, and metastasis.
As a small RNA molecule, miRNA can regulate gene expression at the post-transcriptional level by interacting with mRNA targets. It was found that miR-296-3p downregulated SOX4 by targeting the Wnt/β-catenin signaling pathway to produce anti-tumor effects in TNBC [76], while miR-638 downregulation is associated with poor prognosis in BC patients, and its suppression of HOXA9 and the Wnt/β-catenin signaling pathway can inhibit BC progression [77]. Additionally, lncRNAs can serve as regulators of miRNAs involved in the regulation of the Wnt/β-catenin signaling pathway. For instance, lncRNA MICAL2-1 can bind with miR-25 to suppress the development of BC by regulating DKK3 and inhibiting the activation the Wnt/β-catenin signaling pathway [78]. TMED3, a member of the transmembrane emp24 domain-containing (TMED) protein family, plays a crucial role in protein trafficking and secretion. Modulating TMED3 expression can potentially influence the availability and localization of components involved in the β-catenin pathway. Previous studies have shown that overexpression of TMED3 increases the expression of β-catenin and Axin2, as well as the complex formation of downstream target genes in the Wnt/β-catenin signaling pathway. In a BC study, researchers identified lncRNA RP11-283G6.5 as a modulator of the Wnt/β-catenin pathway. They found that RP11-283G6.5 restricts the progression of BC by regulating the miR-188-3p/TMED3 axis within the Wnt/β-catenin signaling pathway [79], while circ_0008784 can regulate the pathway and promote TNBC cell progression via miR-506-3p-mediated regulation of CTNNB1 [80]. It was also reported that LINC00511-encoding small peptide LINC00511-133 aa restricts apoptosis by regulating the expression levels of Wnt/β-catenin signaling-pathway-related proteins Bax, c-myc, and CyclinD1 and promotes β-catenin into the nucleus, ultimately affecting BC cell invasion and stemness [81].
In addition, ncRNAs also play an important role in the treatment and resistance of BC. Apatinib can inhibit BC development by blocking the Wnt/β-catenin signaling pathway through downregulation of lncRNA ROR [82]. In BC cells surviving after chemotherapy, chemotherapeutic agents, such as doxorubicin or paclitaxel, can activate the EZH2/STAT3 axis in BC cells, leading to the secretion of exosomes rich in miR-378a-3p and miR-378d, which can induce drug resistance by targeting DKK3 and activating the Wnt/β-catenin signaling pathway [83]. Additionally, FSTL1 in BC cells can activate the Wnt/β-catenin signaling pathway via integrin β3, and miR-137 can downregulate FSTL1 mRNA and protein levels to form a miR-137/FSTL1/integrin β3/Wnt/β-catenin signaling axis, regulating BC stemness and chemoresistance [84].
Ultimately, the ncRNAs associated with the Wnt/β-catenin signaling pathway plays an important regulatory role in BC. These ncRNAs affect the proliferation, invasion, metastasis, and stem-cell properties of BC cells by directly or indirectly regulating Wnt/β-catenin signaling. Moreover, they are involved in the regulation of drug resistance and immune escape in BC cells. A deeper understanding of the mechanisms of these ncRNAs in BC will help to reveal the molecular basis of BC development and provide new strategies and targets for precision therapy and personalized medicine. However, many questions still need to be further investigated, including the interaction of ncRNAs with the Wnt/β-catenin signaling pathway, its regulatory effects in the tumor microenvironment, and its potential and limitations in clinical application. Through continuous intensive research, we hope to reveal more details about the occurrence and development of BC and provide more precise methods and strategies for its treatment and prevention.

3.2. The Effect of the Interaction between ncRNA and Wnt/β-Catenin Signaling Pathway on Lung Cancer

The study of Wnt/β-catenin signaling pathway in lung cancer (LC) is increasingly valued, and the role of the ncRNA involved in this tumor is gradually revealed. Lung cancer is a highly heterogeneous and lethal disease, and understanding the function and mechanism of the Wnt/β-catenin signaling-pathway-related ncRNAs in lung cancer is essential to revealing the molecular basis of its occurrence and development and for the development of new therapeutic strategies [85].
MiR-590 is a type of miRNA that commonly exhibits abnormal expression in various tumors. Ma et al. found that this miRNA is downregulated in non-small-cell LC (NSCLC) and closely related to patient prognosis [86]. Overexpression of miR-590 can inhibit the proliferation and invasion of NSCLC cells by targeting GAB1 [87]. On the other hand, miR-590 also regulates LC progression by targeting YAP1 and inhibiting the activation of the Wnt/β-catenin signaling pathway [88].
Another ncRNA related to the Wnt/β-catenin signaling pathway is lncRNA SNHG11 [89]. Its expression is highly upregulated in LC and plays a role in promoting LC cell proliferation, migration, invasion, and the epithelial–mesenchymal transformation process. The ncRNAs could promote LC progression via the activation of the Wnt/β-catenin signaling pathway in two different modes while inhibiting apoptosis. Moreover, lncRNA SNHG11 overexpression was correlated with the poor prognosis, TNM stage, and tumor size of LC patients. LncRNA FLVCR1-AS1 is another ncRNA that was found to regulate the Wnt/β-catenin signaling pathway, inhibiting the proliferation, migration, and invasion of LC cells by suppressing the activity of this pathway [90]. When lncRNA FLVCR1-AS1 is silenced, the expression levels of CTNNB1, SOX4, CCND1, CCND2, c-MYC and β-catenin nuclear protein decrease in LC cells.
Several other ncRNAs have also been found to be intimately involved in the initiation and progression with LC [91,92,93,94,95,96,97]. For example, circEIF3I positively regulates NOVA2 expression by sequestering miR-1253 and further modulates the activity of the Wnt/β-catenin signaling pathway, promoting LC progression. In addition, the low expression of miR-448 inhibits the activation of the Wnt/β-catenin signaling pathway, promoting the proliferation of LC cells and platinum resistance. Furthermore, the suppression of miR-140-5p induces the activation of the Wnt/β-catenin signaling pathway, ensuring platinum resistance in LC cells.
Thus, Wnt/β-catenin signaling activation favors lung cancer progression. Potential therapeutic strategies could be focused on targeting Wnt signaling or ncRNA as an upstream mediator. The limitations of the current experiments are their emphasis on oncogenic ncRNA and the increased effort required to identify the tumor-suppressor ncRNAs regulating Wnt signaling in lung cancer.

3.3. The Effect of the Interaction between ncRNA and Wnt/β-Catenin Signaling Pathway on Colorectal Cancer

Colorectal cancer (CRC) is a common cancer with a high incidence in both men and women [1]. Despite advances in surgery, radiation, and chemo, there are still many challenges in the treatment of CRC [98]. The Wnt signaling pathway is thought to be the major disruption pathway in this malignancy. The ncRNA is thought to promote CRC pathogenesis by triggering or hindering the Wnt signaling pathway.
MiRNAs are a class of short-chain RNAs with a length of 20–24 nucleotides that have been found to be important regulators in various tumors. Studies have found that miRNA-621 directly targets LEF1 and inhibits Wnt/β-catenin signaling, thereby playing a role in the inhibition of metastasis in CRC [99]. Other than miRNAs, lncRNAs and circRNAs also play important regulatory roles in CRC. LINC00665 upregulates CTNNB1 to activate the Wnt/β-catenin signaling pathway and stimulate the tumorigenicity of CRC, promoting tumor progression in the colon [100], and SNHG 4 promotes the progression of colorectal cancer by enhancing RNF15 mRNA stability and activating the Wnt/β-catenin pathway [101]. Conversely, hsa_circ_0026628 plays an inhibitory role in CRC cell proliferation, migration, and EMT focusing on SP1 to inhibit the Wnt/β-catenin pathway [102]. Furthermore, LNC00689 participates in the proliferation, chemotherapy resistance, and metastasis of CRC through the miR-31-5p/YAP/β-catenin axis [103]. In CRC tissues and cells, the downregulation of LINC00689 and upregulation of its downstream target miR-31-5p degrades LATS2, activates the YAP1/β-catenin signaling pathway, and accelerates the development of CRC. Therefore, LINC00689 may be an ideal potential target and positive prognostic factor for 5-fluorouracil (5-FU) chemotherapy in the treatment of CRC. Similarly, hsa_circ_0001666 interferes with Wnt/β-catenin signaling by targeting PCDH10 through miR-576-5p, inhibiting CRC cell proliferation, invasion, and metastasis; inducing apoptosis; and suppressing EMT and stem cells [104]. These results indicate that lncRNAs and circRNAs participate in the regulation of the Wnt/β-catenin signaling pathway to regulate the biological behavior and chemotherapy sensitivity of CRC.
Overexpression of SNHG15, located on chromosome 7p13, has been associated with low survival rates in many human malignancies, including CRC [105,106]. Recent studies have shown that SNHG15 has a critical role in regulating various pathways associated with tumor progression, including Wnt/β-catenin signaling pathway and EMT regulation of CRC [107]. SNHG15 mediates CRC by regulating target gene multiplication, aggression, and migration, along with resistance to colorectal cancer therapy [108,109,110]. Alternative research has also shown that overexpression with SNHG15 adds to drug resistance in CRC cells through strong binding with the translocator MYC [109]. Additionally, SNHG15 is further associated with EMT and colon cancer proliferation through slug–protein interaction [110]. These results suggest that SNHG15 has an essential function to play in CRC by participating in the regulation of the Wnt/β-catenin signaling pathway and other pathways.
Cancer pathogenesis is correlated with lncRNA expression, and several approaches have been proposed to target lncRNA for cancer therapy [111]. One such approach is the knockdown of lncRNA by the post-transcriptional RNA degradation pathway. Specific methods include targeting lncRNA using small interfering RNA (siRNA) through dichotomous and agonamic acid (AGO)-dependent cleavage pathways. Another method is to use antisense oligonucleotides (ASOs) with chemical modifications or gaps to degrade RNA by forming RNA–RNA or RNA–RNA hybrids by the ribonuclease H (RNase-H) mechanism. Furthermore, transcription blockade is an alternative strategy that could permanently or partially delete lncRNA target regions in lncRNA genomic sites by the CRISPR/Cas 9 editing system or block lncRNA expression by insertion of a polyadenylation signal. Modified ASO or RNA-bound small molecules can also be used to interfere with lncRNA–protein interactions, thus enabling inhibition of lncRNA function. Each of these methods can be applied to SNHG15 in CRC to improve the impact on CRC progression.

3.4. The Effect of Interaction between ncRNA and Wnt/β-Catenin Signaling Pathway on Prostate Cancer

Prostate cancer (PCa) is a prevalent malignant tumor and remains one of the primary threats to male health [112]. Although various treatment approaches have emerged in recent years, the prognosis and survival rates for this disease remain suboptimal [113,114]. Several studies have reported the mechanisms associated with ncRNAs in PCa. Through the integration of gene chip technology, second-generation sequencing, and data mining, multiple ncRNAs related to the occurrence and progression of PCa have been identified, including microRNA-4429, microRNA-596, microRNA-301a-3p, microRNA-3648, miR-29a-3p, miR-212-5p, miR-30a-5p, miR-324-3p, miR-452-5p, circPHF16, circITCH, lncRNA SNHG7, lncRNA LEF1-AS1, lncRNA HOTAIRM1, and LINC00115, among others [111,115,116,117,118,119,120,121,122,123,124]. It was found that these ncRNAs regulate biological processes, such as cell proliferation, invasion, metastasis, and epigenetics, and play an essential part in PCa development.
Among these ncRNAs, certain microRNAs exert inhibitory effects on the development of PCa through mechanisms such as targeting SLC39A7 and suppressing the Wnt/β-catenin signaling pathway. For example, miR-15a-3p inhibits the proliferation, invasion, and EMT of PCa cells by targeting SLC39A7 and suppressing the Wnt/β-catenin signaling pathway, providing novel therapeutic targets for PCa treatment [125]. Moreover, several studies have revealed that the overexpression of miR-34a exerts inhibitory effects on the Wnt/β-catenin signaling pathway by modulating the transcriptional activity of Wnt1. This, in turn, leads to the suppression of prostate cancer (PCa) cell proliferation, induces cell-cycle arrest at the G2 phase, and ultimately enhances apoptosis in PCa cells [126].
LncRNAs are another important category of ncRNAs in PCa. LncRNA SNHG7 is highly expressed in PCa cells and acts as a sponge for miRNA-324-3p. Through sponge effects, upregulated SNHG7 positively regulates WNT2B, while downregulation of SNHG7 inhibits EMT in PCa, further suppressing cell proliferation, invasion, and metastasis [120]; lncRNA TMPO-AS1 acts as a scaffold to enhance the interaction between CSNK2A1 and DDX3X and activates the Wnt/β-catenin signaling pathway, thereby promoting the bone metastasis of PCa [127]. On the other hand, circPHF16 is downregulated in PCa tissue. It was found that circPHF16 directly interacted with miR-581, which led to the downregulation of no-name finger protein 128 (RNF128), and activated Wnt/β-catenin signals and inhibited metastasis of PCa [119].
In recent studies, there has been a growing interest among researchers in exploring the issue of drug resistance in PCa; there is also research focused on the issue of drug resistance in PCa. Currently, cisplatin is widely used in the treatment of PCa, but cisplatin resistance remains a significant obstacle to cisplatin-based chemotherapy. Studies have found that upregulation of miR-425-5p sensitizes human PCa to cisplatin by targeting GSK3β and inactivating the Wnt/β-catenin signaling pathway, providing a new target for treating PCa, particularly cisplatin-resistant PCa [128].
Immune escape is an important feature in tumor development, which refers to the certain degree of escape ability of tumor cells to attack the immune system, which causes the tumor to be unable to be effectively cleared by the immune system. To suppress PCa progression, anti-tumor immunity is activated, for which cytotoxic T cells are essential. However, lncRNA can induce PD-1 expression, prevent cytotoxic T-cell proliferation and mediate their apoptosis, leading to immune escape from PCa [129]. Therefore, for effective immunotherapy, it is necessary to identify this lncRNA to enhance the potential of immunotherapy. Several studies have shown that in prostate cancer, lncRNA and miRNA can regulate the expression of immune-related genes through multiple mechanisms to influence the immune response and tumor escape. ncRNA may play an important role in regulating the immune escape from prostate cancer, but the specific mechanism needs further investigation.

3.5. The Effect of the Interaction between ncRNA and Wnt/β-Catenin Signaling Pathway on Gastric Cancer

Gastric cancer (GC) is a prevalent malignancy, one of the most frequent cancers worldwide, and its incidence and fatality rates are still increasing [130,131,132]. Currently, surgery and chemotherapy are the main treatment methods for GC [132]. However, drug resistance remains a limiting factor in chemotherapy, driving researchers to seek new treatment approaches and targets [133]. Recently, increasing studies have shown that ncRNAs can act as dual-acting regulators to directly or indirectly activate or inhibit the Wnt/β-catenin pathway, involved in GC progression [134].
Research has revealed upregulated expression of certain miRNAs, such as miR-150, miR-876-5p, miR-15a-3p, and miR-216a-3p [135,136], while others, including miR-507, miR-23b-3p, miR-520F-3p, and miR-130a-5p, exhibit downregulated expression [136,137,138]. This may have important implications for the diagnosis and prognosis of GC. The discovery of these miRNAs has important implications in the diagnosis and prognosis of GC. Furthermore, several ncRNAs can interact with specific genes. For instance, miR-100, miR-196b, miR-451, miR-185, miR-130a, miR-122-5p, miR-124, miR-451a, and miR-519b-3p can promote the sensitivity of GC cells to radiotherapy by binding with the corresponding target genes [139].
Additionally, ncRNAs are involved in regulating the Wnt/β-catenin pathway, which has a vital role to play in the development and evolution of GC. For example, circCNIH4 and lncRNA NNT-AS1 inhibited apoptosis in GC cells by inactivating the Wnt/β-catenin pathway, while circSmad4, circHIPK3, circAXIN1, and LINC0035 promoted GC advancement and suggested poor prognosis through activation of the Wnt/β-catenin pathway [140,141,142,143,144,145,146]. Some ncRNAs also regulate GC progression through the ceRNA mechanism. For example, circ0005654 is super-regulated and engaged in the miR-363/sp1/myc/Wnt/β-catenin axis in GC tissues and cells to regulate GC cell proliferation and invasion [147]. Circ0091741 sequesters miR-330-3p, upregulating TRIM14 to stabilize Dvl2, thereby activating the Wnt/β-catenin signaling pathway and promoting autophagy and chemotherapy resistance in GC cells [148]. MiRNA-324-5p activates the Wnt signaling pathway by targeting SUFU, enhancing GC cell proliferation, migration, and inducing EMT [144]. LncRNA VIM-AS1 exhibits high expression in GC tissues and cell lines and promotes GC cell proliferation, migration, invasion, and mesenchymal transition by regulating FDZ1 and activating the Wnt/β-catenin signaling pathway [149]. Additionally, studies have shown that LncRNA SUMO1P3 enhances cell invasion, migration, and cell-cycle processes by strengthening the Wnt/β-catenin signaling pathway [150], whereas miR-6838-5p affects GC cell growth, migration, and invasion through the Wnt/β-catenin signaling pathway by targeting Gprin3 [151].
Although numerous studies have evaluated the underlying molecular mechanisms associated with Wnt/β-catenin-mediated GC and investigated a number of treatments that inhibit this oncogenic pathway, elimination of several drawbacks in therapies targeting Wnt/β-catenin, such as drug resistance or non-responsiveness to signaling requires further investigation. As described in this study, many ncRNAs, as dual-acting regulators, can directly or indirectly activate or inhibit the Wnt/β-catenin pathway, and the interaction between these ncRNA and Wnt/β-catenin signaling pathways seems to be a key mechanism in regulating GC. Thus, targeting the circRNA/lncRNA/miRNA/β-catenin axis may be a promising alternative to other targeted therapies based on Wnt/β-catenin signaling.

4. Perspective

Despite significant progress in understanding the mechanisms of action of ncRNAs for Wnt/β-catenin signaling-pathway-associated cancers, many therapeutic challenges remain [152,153]. The regulation of the Wnt/β-catenin signaling pathway by ncRNAs has significant potential value in cancer treatment, but current studies are still in the early stages. Efforts are being made to overcome these challenges by exploring new treatment strategies and methods to open up new avenues for cancer treatment.
The Wnt/β-catenin signaling pathway plays a critical role in various types of cancers, including colorectal cancer, breast cancer, and lung cancer. ncRNAs have been extensively studied and shown to play a key role in regulating cellular biological processes. Here are some suggestions for ncRNA-based therapies targeting the Wnt/β-catenin signaling pathway in cancer:
miRNA-based therapy: Introducing miRNAs that inhibit the activation of the Wnt/β-catenin signaling pathway can effectively suppress the growth and spread of related tumors. For example, miR-34a and miR-200 families have been shown to inhibit β-catenin expression, thereby suppressing the Wnt/β-catenin signaling pathway. Currently, in phase I clinical trials, researchers have successfully delivered synthetic miR-34a mimics to the liver using lipid nanoparticle delivery systems, precisely targeting cancer tissues and regulating the expression of various tumor-suppressor genes such as p53. Therefore, synthesizing miRNA mimics or utilizing delivery systems carrying these miRNAs could be a potential therapeutic strategy.
circRNA regulation: circRNAs have also been found to be associated with the Wnt/β-catenin signaling pathway in cancer. Through techniques such as bioinformatics analysis and high-throughput sequencing, key circRNAs relevant to the Wnt/β-catenin signaling pathway can be identified and validated. Their expression levels and functions in cancer can be experimentally validated. In the functional studies and mechanism elucidation phase, researchers can determine the specific functions and molecular mechanisms of these relevant circRNAs in tumor growth, proliferation, metastasis, and drug resistance. Once the functions and mechanisms of key circRNAs are confirmed, therapeutic strategies targeting circRNAs can be considered. RNA interference (RNAi) and the CRISPR-Cas9 editing system are commonly used techniques for circRNA targeting. RNAi can guide the degradation or inhibition of circRNAs by designing and synthesizing specific small RNA molecules, such as siRNAs or shRNAs. This can be achieved through in vitro transfection or in vivo delivery of RNAi molecules. The CRISPR-Cas9 editing system can induce DNA double-strand breaks on the circular structure of circRNAs using specific oligonucleotide sequences, leading to their degradation. Additionally, the CRISPR-Cas9 system can be used to genetically edit key regulatory genes to further modulate the activity of the Wnt/β-catenin signaling pathway.
lncRNA-targeted therapy: Many lncRNAs have been found to play important roles in controlling the Wnt/β-catenin signaling pathway. By designing appropriate off-target approaches, the functions of these lncRNAs can be selectively interfered with to regulate the activity of the Wnt/β-catenin signaling pathway. Specifically, targeted interventions using RNAi technology and the CRISPR-Cas9 editing system can selectively reduce or inhibit the expression of relevant lncRNAs. For example, an engineered nanoparticle platform delivering lncAFAP1-AS1 siRNA effectively reversed the radioresistance of TNBC. In addition to nanoparticle-based drug delivery systems, recent research has also proposed the therapeutic potential of using the CRISPR/Cas9 system to edit LncRNA expression in CRC patients, and relevant exploration is underway.
Combination therapy: Combination therapy is a strategy that integrates ncRNA-based therapy with other conventional treatment modalities, including chemotherapy, targeted therapy, and immunotherapy, aiming to enhance the effectiveness of cancer treatment. By simultaneously targeting the Wnt/β-catenin signaling pathway and other oncogenic signaling pathways, combination therapy can comprehensively target cancer and offer several advantages. Firstly, combination therapy can overcome resistance issues. Some tumors develop resistance to chemotherapy drugs, but by utilizing ncRNA-based therapy, tumor sensitivity to drugs can be enhanced, effectively addressing drug resistance. Secondly, ncRNA-based therapy and other conventional treatment modalities typically inhibit tumor growth and spread through different mechanisms. Therefore, combining them can achieve synergistic effects on multiple targets, leading to more effective control of tumor development. Additionally, ncRNA-based therapy generally has lower toxicity and side effects, so combining it with conventional treatment methods can reduce the side effects associated with therapy and improve the quality of life for patients. Finally, combination therapy employs a comprehensive treatment approach, combining different treatment modalities that can act on tumors at different levels and time points. This integrated treatment strategy can comprehensively suppress tumors and improve the overall effectiveness of treatment.
The diverse mechanisms by which ncRNAs regulate the Wnt/β-catenin signaling pathway represent potential therapeutic targets for cancer treatment. Further research is needed to identify specific ncRNAs and their potential mechanisms in different types of cancer, as well as to develop more effective delivery strategies. Overall, studying ncRNAs in Wnt/β-catenin signaling-pathway-associated cancers has great potential to improve cancer diagnosis and treatment.

Author Contributions

Conceptualization, L.G. and T.L.; investigation, X.Y. (Xinbing Yang), Y.D., L.L., X.X., S.X. and X.Y. (Xueni Yang); writing—original draft preparation, X.Y. (Xinbing Yang), L.G. and T.L.; writing—review and editing, L.G. and T.L.; supervision, T.L.; funding acquisition, L.G. and T.L. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by National Natural Science Foundation of China (No. 62171236), the key project of social development in Jiangsu Province (No. BE2022799), the key projects of Natural Science Research in Universities of Jiangsu Province (22KJA180006), and the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Regulation of Wnt/β-catenin Signaling Pathway by ncRNAs: Insights into Activation and Suppression Mechanisms (By Figdraw). “Activation State”: when Wnt binds to drizzled and LRP receptors, cytoplasmic protein DVL is activated, leading to the inhibition of GSK3β. Subsequently, stabilized β-catenin translocates into the nucleus and interacts with TCF/LEF transcription factors, resulting in target gene transcription. In this activation mechanism, specific ncRNAs, such as miR-34a and miR-27a, play pivotal roles. They interact with the promoter region of Wnt genes, promoting the transcription and expression of Wnt proteins, thus enhancing Wnt protein levels. Additionally, they interact with negative regulators in the Wnt/β-catenin signaling pathway, such as Axin and GSK-3β, reducing their degradation effect on β-catenin. Furthermore, ncRNAs like circHIPK3 also modulate key genes in the pathway, decreasing their degradation effect on β-catenin and promoting the activation of the Wnt/β-catenin signaling pathway, thereby enhancing its activity. “Suppression State”: in the absence of WNT ligands, the destruction complex of β-catenin consists of AXIN, CK1α, GSK3β, and APC, which phosphorylate β-catenin for subsequent ubiquitin–proteasome degradation. In the suppression mechanism, certain ncRNAs, such as miR-425-5p and circ_0026628, play essential roles. They interact with negative regulators in the Wnt/β-catenin signaling pathway, such as Axin and GSK-3β, and enhance their degradation effect on β-catenin. This leads to increased degradation of β-catenin, resulting in the inhibition of signaling pathway activity. Moreover, ncRNAs like circ_0026628 can also interact with regulatory factors associated with downstream genes in the Wnt/β-catenin signaling pathway, inhibiting their transcriptional activity and reducing the transcription levels of downstream genes. These interactions further enhance the degradation of β-catenin, ultimately influencing the activity state of the signaling pathway. ncRNAs highlighted in red font signify the activation of the Wnt signaling pathway, whereas those in blue font represent inhibition of the Wnt signaling pathway.
Figure 1. Regulation of Wnt/β-catenin Signaling Pathway by ncRNAs: Insights into Activation and Suppression Mechanisms (By Figdraw). “Activation State”: when Wnt binds to drizzled and LRP receptors, cytoplasmic protein DVL is activated, leading to the inhibition of GSK3β. Subsequently, stabilized β-catenin translocates into the nucleus and interacts with TCF/LEF transcription factors, resulting in target gene transcription. In this activation mechanism, specific ncRNAs, such as miR-34a and miR-27a, play pivotal roles. They interact with the promoter region of Wnt genes, promoting the transcription and expression of Wnt proteins, thus enhancing Wnt protein levels. Additionally, they interact with negative regulators in the Wnt/β-catenin signaling pathway, such as Axin and GSK-3β, reducing their degradation effect on β-catenin. Furthermore, ncRNAs like circHIPK3 also modulate key genes in the pathway, decreasing their degradation effect on β-catenin and promoting the activation of the Wnt/β-catenin signaling pathway, thereby enhancing its activity. “Suppression State”: in the absence of WNT ligands, the destruction complex of β-catenin consists of AXIN, CK1α, GSK3β, and APC, which phosphorylate β-catenin for subsequent ubiquitin–proteasome degradation. In the suppression mechanism, certain ncRNAs, such as miR-425-5p and circ_0026628, play essential roles. They interact with negative regulators in the Wnt/β-catenin signaling pathway, such as Axin and GSK-3β, and enhance their degradation effect on β-catenin. This leads to increased degradation of β-catenin, resulting in the inhibition of signaling pathway activity. Moreover, ncRNAs like circ_0026628 can also interact with regulatory factors associated with downstream genes in the Wnt/β-catenin signaling pathway, inhibiting their transcriptional activity and reducing the transcription levels of downstream genes. These interactions further enhance the degradation of β-catenin, ultimately influencing the activity state of the signaling pathway. ncRNAs highlighted in red font signify the activation of the Wnt signaling pathway, whereas those in blue font represent inhibition of the Wnt signaling pathway.
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Table 1. Research overview of ncRNAs and Wnt/β-catenin signaling pathway in cancers (Activation: activation of the Wnt signaling pathway; Suppression: inhibition of the Wnt signaling pathway).
Table 1. Research overview of ncRNAs and Wnt/β-catenin signaling pathway in cancers (Activation: activation of the Wnt signaling pathway; Suppression: inhibition of the Wnt signaling pathway).
Cancer TypencRNAsExpressionMechanismsFunctions to Wnt PathwayPMID
Breast cancermiR-125bUpWnt/β-cateninActivation30950326
miR-296-3pDownSOX4Suppression34785625
miR-96-5pDownCTNND1Suppression31913290
miR-9501Upβ-cateninSuppression32373971
miR-548c-5pDownWnt1Suppression32329856
miR-516a-3pDownPygopus2Suppression31273950
miR-454-3pUpRPRD1AActivation30809286
miR-449b-5pDownCREPTSuppression30738779
miR-429DownWnt/β-cateninSuppression32961031
miR-34aUpWnt3/Wnt1Activation30779084
miR-340-5pDownLGR5Suppression30300682
miR-296DownFGFR1Suppression31841196
miR-27aUpGSK-3βActivation33025840
miR-216aDownWnt/β-cateninSuppression30864744
miR-193bDownc-MetSuppression34863149
miR-190DownSOX9Activation30658681
miR-135DownWnt/β-cateninSuppression35730603
miR-130a-3pDownNRARPSuppression35797350
miR-124-3p.1UpAxin1Activation32125723
lncRNA MICAL2-1DownmiR-25/DKK3Suppression34970696
lncRNA RP11-283G6.5DownmiR-188-3p/TMED3Suppression34416888
lncRNA RUSC1-AS-NUpWnt1/β-cateninActivation30569097
lncRNA RBM5-AS1UpWnt/β-cateninActivation35110544
lncRNA HOTTIPUpmiR-148a-3p/WNT1Activation32307830
lncRNA HOTTIPUpWnt/β-cateninActivation30676763
lncRNA H19UpmiR-340-3p/YWHAZActivation30676763
lncRNA C5orf66-AS1UpmiR-149-5p/CTCF/CTNNB1Activation35499320
lncRNA ASMTL-AS1DownmiR-1228-3p/SOX17Suppression34006305
lncRNA LUCAT1UpmiR-5582-3p/TCF7L2Activation31300015
lncRNA CCAT1UpmiR-204/211/miR-148a/152/ANXA2Activation31695775
LINC01287UpWnt/β-cateninActivation31173295
LINC01234UpmiR-525-5p/MEIS2Activation34173712
circ_0008784UpmiR-506-3p/CTNNB1Activation36436315
circ-ITCHDownmiR-214/miR-17Activation30509108
circARL8BUpmiR-653-5p/HMGA2Activation34050452
circABCC4UpmiR-154-5pSuppression34050452
Lung cancermiR-590DownYAP1Suppression35031966
miR-448DownSATB1Activation32525527
miR-489-3pUpUSP48Activation35413838
miR-421UpHOPXActivation 31115507
miR-23BDownRUNX2Suppression32495614
miR-20bDownAPCActivation31894264
miR-1b-19pDownMYPT3Suppression33964297
miR-147bDownRPS15ASuppression31665807
miR-103UpKLF7Activation32582959
miR-100DownHOXA1Suppression32364673
miR-520aUpRRM2Suppression33859925
lncRNA SNHG11UpmiR-4436a/CTNNB1Activation32239719
lncRNA FLVCR1-AS1UpWnt/β-cateninSuppression30697812
lncRNA-SNHG7DownmiR-181/cbx7Suppression32201260
lncRNASEH1-AS1UpmiR-516a-5p/FOXK1Activation35166053
lncRNA SNHG20UpmiR-197/TCF/LEF1Activation31957836
lncRNA PVT1UpmiR-361-3p/SOX9Activation32197208
lncRNA JPXUpmiR-33a-5p/Twist1Activation32197208
lncRNA HJURPUpβ-cateninSuppression31115012
LncRNA DSCAM-AS1UpmiR-577/HMGB1Activation32386483
lncRNA AWPPHUpWnt/β-cateninActivation32386483
LncDBH-AS1DownmiR-155/AXIN1Activation33506901
LINC01006UpmiR-129-2-3p/CTNNB1Activation33753463
LINC00942UpmiR-5006-5p/FZD1Activation34253104
LINC00669UpWnt/β-cateninActivation36621836
LINC00326UpmiR-657/DKK2Suppression36747258
LINC00673-v4UpDDX3/CK1εActivation31235588
circ-EIF3IUpmiR-1253/NOVA2Activation36193788
has_circ_0017109UpmiR-671-5p/FZD4Activation36434577
has_circ_0001946UpmiR-135a-5p/SIRT1Activation30841451
hsa_circ_0066903DownmiR-3681-3p/miR-3909/GSK3BSuppression35821283
hsa_circ_0007059DownmiR-378Suppression31351967
has_circ_0006427DownmiR-6783-3p/DKK1Suppression30470570
circ-ZNF124UpmiR-498/YES1Suppression33186139
circVAPAUpmiR-876-5p/WNT5aActivation33619796
circ-PGCUpmiR-2-532p/FOXR3Activation34494941
circ_0067934UpmiR-1182/KLF8Activation32768951
Colorectal cancermiR-621DownLEF1Suppression36087740
miR-576-5pUpWnt5aActivation33300054
miR-532-3pDownETS3/TGM1Suppression31570702
miR-501-3pUpAPCActivation31364752
miR-381DownSPIN1Activation34753384
miR-377-3pDownZEB2/XIAPSuppression32220639
miR-30-5pDownUSP2Suppression30338942
miR-19a-3pUpFOXF2Suppression32103872
miR-188UpFOXL1Activation37305399
miR-183-5pUpRCN2Suppression30896885
miR-144-3pDownBCL6Suppression32206063
miR-103/107UpAxin2Activation31273221
miR-6125DownYTHDF2Activation34709763
miR-520eDownAEG-1Suppression31574178
LINC00665UpmiR-214-3p/CTNNB1Activation33865827
lncRNA TUG1UpmiR-542-3p/TRIB2Activation34030715
lncRNA PART1UpmiR-150-5p/miR-520h/CTNNB1Activation31669140
lncRNA NEAT1UpmiR-486-5p/NR4A1Activation33337350
lncRNA NEAT1UpmiR-34a/SIRT1Activation30312725
lncRNA HCG18UpmiR-1271/MTDHActivation31854468
lncRNA ADAMTS9-AS1DownWnt/β-cateninSuppression32889785
LINC01315UpWnt/β-cateninActivation35322763
LINC00963-v2/-v3DownmiR-143/miR-217/miR-512/APC/AxinSuppression36804476
LINC00365UpCDK1Activation31544991
circ_0082182UpmiR-411/miR-1205Activation33596920
hsa_circ_0026628UpmiR-346/SP1Activation34420031
hsa_circ_0068464UpmiR-383Activation35168468
hsa_circ_0009361DownmiR-582/APC2Suppression31109967
hsa_circ_0005615UpmiR-149-5p/TNKSActivation32393760
hsa_circ_0005075UpWnt/β-cateninActivation31081084
circRASSF2UpmiR-195-5p/FZD4Activation33929991
circPTK2UpmiR-136-5p/YTHDF1Activation34974791
circ-IGF1RUpmiR-362-5p/HMGB3Activation36542208
circIFT80UpmiR-142/miR-568/miR-634/CTNNB1Activation35783013
circAGFG1UpmiR-4262/miR-185-5/pYY1/CTNNB1Activation32681092
circ-ACAP2UpmiR-143-3p/FZD4Activation34085707
circ_0026344DownmiR-183Suppression31608699
Prostate cancermiR-4429DownDLX1Suppression33740948
miR-596Downβ-cateninSuppression33387246
miR-15a-3pDownSLC39A7Suppression31135177
miR-34aDownWnt1Suppression32894541
miR-425-5pDownGSK3βSuppression31502580
miR-653-5pDownSOX30Suppression31889959
miR-95-3pUpDKK3Activation30779066
lncRNA SOX2-OTUpmiR-452-5p/HMGB3Suppression32407168
lncRNA SNHG12UpmiR-195Activation30945357
lncRNA HOTTIPUpWnt/β-cateninSuppression30809864
LINC00115UpmiR-212-5p/FZD5Activation34697900
circPHF16DownmiR-581/RNF128Suppression36503162
Gastric cancermiRNA-150UpSUFUActivation33848981
miR-520f-3pDownSOX9Suppression32277152
miR-507DownCBX4Suppression35819589
miR-324-5pUpSUFUActivation33017570
miR-6838-5pDownGPRIN3Suppression33254176
miR-192/-215UpAPCActivation32091625
miR-188-5pUpPTENActivation31138169
miR-195-5pDownYAPActivation31378888
miR-381/miR-489DownCUL4BSuppression30483755
miR-675UpPITX1Activation31260797
LINC00355UpWnt/β-cateninActivation32894544
lncRNA NNT-AS1UpmiR-142-5p/SOX4Activation32468065
lncRNA VIM-AS1UpmiR-8052/FDZ1Activation33173977
lncRNA SUMO1P3UpWnt/β-cateninActivation33179980
LINC01225UpWnt/β-cateninActivation31460694
LINC01503UpWnt/β-cateninActivation32207034
lncRNA H19Upβ-cateninActivation34348271
lncRNA MIR4435-2HGUpDSPActivation31484163
lncRNA NCK1-AS1UpmiR-22-3p/BCL9Activation33974352
lncRNA SNHG11UpmiR-483-3p/miR-1276/CTNNB1/ATG12Activation33068778
lncRNA ZEB2-AS1UpWnt/β-cateninActivation30635820
lncRNA ZFAS1UpmiR-200b/Wnt1Activation30999814
LOC100505817DownWnt/β-cateninActivation34385891
LOC285194DownWnt/β-cateninSuppression31991056
circ0005654UpmiR-363/sp1Activation34499009
circ_0091741UpmiR-330-3p/TRIM14Activation36323918
circ-SFMBT2UpmiR-885-3p/CHD7Activation34387601
cir-ITCHDownmiR-17Suppression33060778
hsa_circ_0001649DownmiR-20a/ERKSuppression32212290
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MDPI and ACS Style

Yang, X.; Du, Y.; Luo, L.; Xu, X.; Xiong, S.; Yang, X.; Guo, L.; Liang, T. Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/β-Catenin Signaling Pathway in Tumor Progression. Int. J. Mol. Sci. 2023, 24, 13909. https://doi.org/10.3390/ijms241813909

AMA Style

Yang X, Du Y, Luo L, Xu X, Xiong S, Yang X, Guo L, Liang T. Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/β-Catenin Signaling Pathway in Tumor Progression. International Journal of Molecular Sciences. 2023; 24(18):13909. https://doi.org/10.3390/ijms241813909

Chicago/Turabian Style

Yang, Xinbing, Yajing Du, Lulu Luo, Xinru Xu, Shizheng Xiong, Xueni Yang, Li Guo, and Tingming Liang. 2023. "Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/β-Catenin Signaling Pathway in Tumor Progression" International Journal of Molecular Sciences 24, no. 18: 13909. https://doi.org/10.3390/ijms241813909

APA Style

Yang, X., Du, Y., Luo, L., Xu, X., Xiong, S., Yang, X., Guo, L., & Liang, T. (2023). Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/β-Catenin Signaling Pathway in Tumor Progression. International Journal of Molecular Sciences, 24(18), 13909. https://doi.org/10.3390/ijms241813909

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