Search Results (1,920)

As with other non-coding RNAs (ncRNAs), the aberrant expression of long non-coding RNAs (lncRNAs) can be associated with different forms of cancers, including breast cancer (BC). Various lncRNAs may either promote or suppress cell proliferation, metastasis, and other related cancer signaling pathways by interacting with other cellular machinery, thus affecting the expression of BC-related genes. However, lncRNAs are characterized by features that are unlike protein-coding genes, which pose unique challenges when it comes to their study and utility. They are highly diverse and may display contradictory functions depending on factors like the BC subtype, isoform diversity, epigenetic regulation, subcellular localization, interactions with various molecular partners, and the tumor microenvironment (TME), which contributes to the intratumoral heterogeneity and phenotypic plasticity. While lncRNAs have potential clinical utility, their functional heterogeneity coupled with a current paucity of knowledge of their functions present challenges for clinical translation. Strategies to address this heterogeneity include improving classification systems, employing CRISPR/Cas tools for functional studies, utilizing single-cell and spatial sequencing technologies, and prioritizing robust targets for therapeutic development. A comprehensive understanding of the lncRNA functional heterogeneity and context-dependent behavior is crucial for advancing BC research and precision medicine. This review discusses the sources of lncRNA heterogeneity, their implications in BC biology, and approaches to resolve knowledge gaps in order to harness lncRNAs for clinical applications. Full article

Intracranial aneurysms (IAs) are potentially devastating cerebrovascular lesions, and predicting rupture risk remains a major clinical challenge. Conventional radiological and clinical scores offer only partial risk stratification, highlighting the need for complementary approaches. Liquid biopsy represents a promising non-invasive strategy to identify circulating biomarkers that reflect aneurysm biology and instability. We conducted a systematic review according to PRISMA 2020 guidelines, screening PubMed, Scopus, and Web of Science up to August 2025. Forty-eight eligible studies, encompassing 3515 IA patients, evaluated circulating RNA species, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in serum, plasma, blood, or cerebrospinal fluid. Multiple candidates emerged as consistently dysregulated: upregulation of miR-21, miR-126, and miR-200a-3p, and downregulation of miR-143 and let-7b-5p were recurrently observed across independent cohorts. LncRNAs, such as MALAT1 and MIAT, and circRNAs, including circ_0000690 and circ_0021001, demonstrated diagnostic and prognostic potential, with some correlating with rupture status and clinical severity indices. Despite encouraging findings, heterogeneity in study design, sample handling, and analytic methods limits reproducibility. Large-scale, multicenter validation studies are essential to translate these biomarkers into clinical practice. Full article

Malignant brain tumors remain highly challenging to treat due to intrinsic and acquired therapy resistance and limited therapeutic options, consequently contributing to poor prognosis. Advancing the understanding of resistance mechanisms alongside novel treatment strategies is essential to improve clinical outcomes. Altered gene expression is common in tumors, and a specific class of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), is frequently deregulated. LncRNAs play critical roles in processes such as cell proliferation, cell cycle arrest, and metastasis in brain cancer, functioning either as tumor promoters or suppressors. They exert their effects through transcriptional and post-transcriptional regulatory mechanisms. Understanding the functional roles of lncRNAs in malignant brain tumors has become a priority, as they are differentially expressed in tumors compared to healthy tissue. These molecules are studied for their potential as therapeutic targets and biomarkers in oncology. This review provides an overview of current research on brain cancer and lncRNAs, emphasizing the need for further investigation into their specific roles in therapy resistance and their involvement in various pathways. A better understanding of lncRNAs and their role in brain cancer could offer valuable insights into their prognostic and therapeutic potential, with the promise of improving early diagnosis and treatment outcomes. Full article

Objectives: MicroRNAs of the miR-200 family are recognized as key inhibitors of epithelial-to-mesenchymal transition (EMT). However, there is limited data on the potential regulation of miR-200 family expression by long non-coding RNAs (lncRNAs) in RCC. Methods: We conducted a comprehensive literature and database search to identify lncRNAs that had been already functionally validated as regulators of any member of the miR-200 family. We analyzed the expression levels of the miR-200 family and the identified lncRNAs by qPCR. The study included 42 samples of carcinoma and non-carcinoma tissue from 25 RCC patients. In addition, we used RNA sequencing data from The Cancer Genome Atlas (TCGA), encompassing 511 kidney RCC (KIRC) samples, to further analyze the expression of miRNAs and lncRNAs. Results: We identified 127 lncRNAs with confirmed regulatory functions, 31 of which were validated in our samples. The majority of lncRNAs, along with all members of the miR-200 family, showed consistent downregulation in carcinoma tissues compared to non-carcinoma tissues. We observed a significant correlation between the expression of at least one member of the miR-200 family and 17 lncRNAs. In particular, three lncRNAs (MALAT1, OIP5-AS1, and LINC00467) showed a correlation with the expression of all members of the miR-200 family. Our results were at least partially confirmed in KIRC samples from the TCGA dataset. Conclusions: Our results suggest that the expression of the miR-200 family in RCC might be at least partially influenced by lncRNAs. Based on our cohort of samples, MALAT1, OIP5-AS1, and LINC00467 appear to be potentially important contributors to RCC development. Full article

Long intergenic non-coding RNA 00511 (LINC00511) has been involved in the development of several types of cancer including breast cancer (BC). Several single nucleotide polymorphisms (SNPs) can be found in the genomic regions of long non-coding RNAs (lncRNAs) and are associated with the tumorigenesis of many cancers. The objective of the current study is to assess whether LINC00511 SNPs (rs11657109, rs9906859, rs17780195, rs1558535, and rs4432291) could be related with BC incidence in the Egyptian population. Five SNPs of LINC00511 were analyzed in a case–control study of 267 BC cases and 150 controls. Logistic regression analysis was used to test the association between LINC00511 SNPs and BC incidence. We found that the TT genotype of rs11657109 significantly increased BC incidence (OR: 2.177, 95%CI: 1.260–3.763) and this SNP was associated with high incidence of luminal A BC specifically using different genetic models. Haplotype (A₀₉ A₉₁ A₃₅ G₉₅ T₅₉) was strongly associated with an increased BC incidence as it was totally absent in controls. These findings suggest that LINC00511 SNP rs11657109 is associated with BC susceptibility in the Egyptian population. Full article

Cerebral ischemia/reperfusion (I/R) injury is a devastating neurological disorder with limited treatment options. Emerging evidence suggests that the N6-methyladenosine (m6A) modification and its regulatory factors play pivotal roles in the pathophysiology of I/R. This study aimed to elucidate the function of METTL3-mediated m6A modification of the long non-coding RNA (lncRNA) AU020206 in ferroptosis during cerebral I/R injury and to identify potential molecular targets for neuroprotection. A murine model of middle cerebral artery occlusion/reperfusion (MCAO/R) and N2a cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) were established to assess m6A levels and ferroptosis-related changes. Effects of METTL3 overexpression and lncRNA-AU020206 silencing on neuronal apoptosis, inflammation, and ferroptosis were investigated in vitro and in vivo. The interaction between lncRNA-AU020206 and YTHDC2 and the resulting regulation of SLC7A11 mRNA stability and GPX4 expression were evaluated using molecular and biochemical assays. Both MCAO/R mice and OGD/R-treated N2a cells exhibited decreased m6A levels and upregulation of lncRNA-AU020206 accompanied by enhanced ferroptosis. METTL3 overexpression increased the m6A modification of AU020206, promoting its degradation and attenuating neuronal injury, whereas silencing AU020206 or overexpressing YTHDC2 decreased SLC7A11 mRNA stability and enhanced ferroptosis. Restoring the expression of SLC7A11/GPX4 can enhance cell viability, alleviate neuronal apoptosis, and reduce Fe²⁺ overload. Disruption of the METTL3–AU020206–YTHDC2 axis abolished these neuroprotective effects. METTL3-mediated m6A modification of lncRNA-AU020206 restrained ferroptosis and neuronal injury in cerebral I/R by maintaining the stability of the SLC7A11/GPX4 axis via interactions with YTHDC2. Targeting this epitranscriptomic signalling pathway may represent a promising therapeutic strategy for the treatment of ischemic stroke and related neurological disorders. Full article

Acute myeloid leukemia (AML) is a highly heterogeneous disease, with significantly higher incidence and fatality rates in the elderly. Even with recent decades of research progress in AML, the exact etiology of this deadly disease is still not fully understood, with recent advancements in sequencing technologies highlighting the role of a growing number of non-coding RNAs (ncRNAs) that are intimately associated with AML leukemogenesis. These ncRNAs have been found to have a significant role in leukemia-related cellular processes such as cell division, proliferation, and death. A few of these non-coding RNAs exhibit potential as prognostic biomarkers. The three main groups of ncRNAs that contribute unique activities, especially in cancer, are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Their existence or altered expression levels frequently offer vital information on the diagnosis, course of treatment, and follow-up of cancer patients. The identification of ncRNAs has opened up new avenues for the diagnosis, prognosis, and therapy of acute myeloid leukemia. In order to provide a clear understanding of the significant influence that lncRNAs have on prognostic predictions and diagnostic accuracy in AML, this review aims to provide a comprehensive and insightful understanding of how these molecules actively participate in the complex landscape of the disease. Full article

Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of the global population, characterized by abnormal keratinocyte proliferation and dysregulated immune responses. This review examines the emerging role of long non-coding RNAs (lncRNAs) in psoriasis pathogenesis, highlighting their significance as regulatory molecules in disease initiation, progression, and chronicity. LncRNAs demonstrate distinct expression patterns in psoriatic lesions, with upregulated transcripts such as MALAT1, XIST, MIR31HG, and HOTAIR promoting keratinocyte hyperproliferation, inhibiting apoptosis, and amplifying inflammatory cascades through mechanisms including microRNA sponging and transcription factor modulation. These molecules primarily target key signaling pathways including NF-κB, STAT3, and PI3K/AKT. Conversely, downregulated lncRNAs like NEAT1, MEG3, and PRINS normally function as tumor suppressor molecules that maintain epidermal homeostasis through pro-apoptotic and anti-inflammatory mechanisms. Their reduced expression contributes to the pathological hyperproliferative phenotype characteristic of psoriatic skin. Importantly, genetic variants within lncRNA loci have been identified as significant contributors to psoriasis susceptibility and treatment responses across different populations. Single- nucleotide polymorphisms in genes such as TRAF3IP2-AS1, HOTAIR, and CDKN2B-AS1 demonstrate population-specific associations with disease risk and therapeutic outcomes, suggesting their potential utility as pharmacogenomic markers. The complex regulatory networks involving lncRNAs provide new insights into psoriasis pathogenesis and offer promising avenues for personalized treatment strategies. Integration of lncRNA profiling into clinical practice may enhance our understanding of disease heterogeneity and improve therapeutic outcomes for psoriatic patients. Full article

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine and metabolic conditions affecting women of reproductive age. This condition affects around 20% of this demographic and is characterized by polycystic ovarian morphology, hyperandrogenism, and chronic anovulation. Obesity, impacting 40–85% of women with PCOS, exacerbates insulin resistance, increases insulin levels, and intensifies low-grade inflammation. This exacerbates the reproductive and metabolic complications associated with the condition. Recent advancements in molecular biology have underscored the significance of non-coding RNAs, including as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as crucial regulators of gene expression and prospective biomarkers for PCOS. Exosome-derived microRNAs (ex-miRNAs) have emerged as compelling candidates due to their stability in body fluids and their capacity to promote intercellular communication among adipose tissue, the ovary, and the endometrium. Research, encompassing both experimental and clinical studies, has shown that ex-miRNAs display differing expression levels in women with obesity-related PCOS. Several of these ex-miRNAs are associated with networks that govern inflammation, glucose metabolism, steroidogenesis, and folliculogenesis. Moreover, the encapsulation of these chemicals within exosomes safeguards them from enzymatic breakdown, hence augmenting their potential as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring. Despite the initial results being encouraging, challenges remain in standardising exosome separation, quantifying miRNA, and analyzing functional data within the complex pathophysiology of PCOS. This narrative review consolidates existing evidence regarding the molecular signatures of obesity-related infertility in PCOS, emphasising the growing significance of exosomal miRNAs and other non-coding RNAs, while examining their translational potential for early diagnosis and personalised therapeutic approaches. Full article

Non-coding RNAs (ncRNAs) are critical regulators of gene expression, taking part in the modulation of multiple biological functions across a range of cell types. Initially dismissed as transcriptional noise, ncRNAs are now recognized for their significant roles in key cellular mechanisms, including differentiation, apoptosis, and proliferation, as well as their profound implications for the pathogenesis of numerous human diseases. Due to their remarkable stability, tissue-specific expression patterns, and abundance in body fluids, ncRNAs hold significant promise as non-invasive biomarkers for diagnosis, prognosis, and therapeutic monitoring. Furthermore, advances in RNA-targeted therapeutics have introduced novel strategies to modulate ncRNA activity, although challenges related to delivery efficiency, specificity, and clinical validation remain. This review comprehensively summarizes the classification, biogenesis, and molecular functions of ncRNAs, elucidates their involvement in health and disease, and evaluates their potential as clinical biomarkers and therapeutic targets. Additionally, it discusses the emerging technologies for RNA manipulation, including CRISPR-based RNA editing, that can advance ncRNA research and revolutionize ncRNA-based therapeutics. Full article

Long non-coding RNAs (lncRNAs) are essential regulatory molecules involved in various biological processes in mammals. However, their expression patterns across multiple porcine tissues have not been systematically characterized. We analyzed 607 RNA-seq datasets derived from 14 porcine tissues, including backfat, gallbladder, heart, ileum, jejunum, kidney, longissimus dorsi, liver, lung, skeletal muscle, ovary, pituitary, skeletal muscle, and spleen. Additionally, we examined 63 single-cell RNA-seq datasets from porcine primary oocytes at five developmental stages. For comparative analysis, we included 20 human and 17 mouse oocyte RNA-seq datasets. We identified 52,798 porcine lncRNAs, with tissue-specific expression patterns most prominent in oocytes and least in skeletal muscle. Among them, 2169 were classified as housekeeping and 14,469 as tissue-specific lncRNAs. Cross-species analysis revealed that a small subset of oocyte-expressed lncRNAs is conserved in humans and mice, associated with catalytic activity and circadian regulation. Additionally, 44 lncRNAs were differentially expressed during oocyte development, implicating them in neurogenesis, vesicle transport, and protein modification. Our findings not only contribute to the growing body of knowledge regarding lncRNAs in porcine biology but also pave the way for future research aimed at elucidating their functional roles in reproductive biology and other physiological processes. Full article

Background: Micropeptides, encoded by non-coding RNAs, play a pivotal role in various cellular functions. While several micropeptides have already been linked to HCC, their roles remain incompletely understood. Our study identifies MP60, a conserved micropeptide strongly associated with HCC progression. Methods and Results: By analyzing The Cancer Genome Atlas (TCGA) dataset, we assessed the coding potential of long non-coding RNAs (lncRNAs) with significant expression changes in HCC. Our findings reveal that ENST0000614292, a transcript of LINC01138, exhibited the highest coding potential, encoding a putative 60-amino-acid micropeptide, which we have named MP60 and confirmed the expression of MP60 in HCC tissues, with a nuclear localization. MP60 directly interacts with RNA-binding motif protein 10 (RBM10) and downregulates its expression. Additionally, MP60 modulates EMT. Functional analyses demonstrated that MP60 promotes cellular proliferation and migration, while reducing cellular adhesion, translated by enhanced tumorigenesis in vivo. Notably, MP60 expression is markedly increased in HCC tissues and is associated with a poorer prognosis. Conclusions: These findings identify MP60 as a potential biomarker and therapeutic target in HCC, linking its oncogenic effects to EMT modulation and tumor progression. Full article

Hepatitis E virus (HEV) is one of the pathogens that cause viral hepatitis, and its clinical symptoms can manifest as acute, chronic viral hepatitis, or asymptomatic infection. Among them, swines are the main animal source of HEV. Open reading frame 3 (ORF3) is a multifunctional protein essential for swine hepatitis E virus (SHEV) infection and release, involved in biological processes such as intracellular signal transduction regulation. In our preliminary research, we utilized adenovirus-mediated overexpression of type IV SHEV ORF3 in HepG2 cells, extracted total RNA, and performed high-throughput long non coding RNAs (lncRNAs) and transcriptome sequencing. In this study, we screened and analyzed lncRNAs involved in the GO pathway: viral process (GO: 0016032), and combined them with differentially expressed mRNAs for target gene prediction. We identified two lncRNAs—lncRNA AL137002 (MSTRG. 7478) and lncRNA AL049840 (MSTRG. 8427)—that are associated with viral progression and have p ≤ 0.05 in HepG2 cells expressing ORF3 of porcine hepatitis E virus type IV. We predicted their five lncRNA-mRNA networks, which are lncRNA AL137002 (MSTRG. 7478)-ENST0000375440, lncRNA AL137002 (MSTRG. 7478)-ENST0000375441, lncRNA AL049840(MSTRG. 8427)-ENST0000246489, lncRNA AL049840 (MSTRG. 8427)-ENST0000554280 and lncRNA AL049840 (MSTRG. 8427)-ENST0000452929, and were used to predict their lncRNA mRNA binding sites and construct relevant molecular models. This will lay a solid foundation for further revealing the function of SHEV ORF3 and elucidating the mechanism of SHEV infection. Full article

Long noncoding RNAs (lncRNAs) have emerged as key regulators of gene expression during seed development and physiology. This review examines the diverse roles of lncRNAs in key stages of seed development, including embryogenesis, maturation, dormancy, germination, and aging. It integrates the current understanding of the biogenesis and classification of lncRNAs, emphasizing their functional mechanisms in seeds, particularly those acting in cis and trans. These mechanisms include the scaffolding of polycomb and SWI/SNF chromatin remodeling complexes, the guidance of RNA-directed DNA methylation, the ability to function as molecular decoys, and the modulation of small RNA pathways via competitive endogenous RNA activity. This review highlights the regulatory influence of lncRNAs on abscisic acid (ABA) and gibberellin (GA) signaling pathways, as well as light-responsive circuits that control dormancy and embryonic root formation. Endosperm imprinting processes that link parental origin to seed size and storage are also discussed. Emerging evidence for epitranscriptomic modifications, such as m6A methylation, and the formation of LncRNA–RNA-binding protein condensates that maintain resting states and coordinate reserve biosynthesis are also reviewed. Advances in methodologies, including single-cell and spatial transcriptomics, nascent transcription, direct RNA sequencing, and RNA–chromatin interaction mapping, are expanding the comprehensive lncRNA landscape during seed development and germination. These advances facilitate functional annotation. Finally, possible translational research applications are explored, with a focus on developing lncRNA-based biomarkers for seed vigor and longevity. Full article

The adult lumbar spinal cord plays a critical role in locomotor control and somatosensory integration, whose transcriptional architecture under physiological conditions has been characterized in various studies with restricted numbers of individuals (up to four). Here, we present an integrative single-nucleus RNA sequencing (snRNA-seq) atlas of the healthy adult mouse lumbar spinal cord, assembled from over 86,000 nuclei from 16 samples across five public datasets. Using a harmonized computational pipeline, we identify all major spinal cell lineages and resolve 17 transcriptionally distinct neuronal subtypes. A central novelty of our approach is the systematic inclusion of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and pseudogenes. By comparing transcriptomic analyses based on coding-only, non-coding-only, and combined gene sets, we show that ncRNAs, despite accounting to a 10% of the recorded information of each cell, contribute to cell type-specific signatures. This resource offers a high-resolution, ncRNA-inclusive reference for the adult spinal cord and provides a foundation for future studies on spinal plasticity, injury, and regeneration. Full article