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Non-coding RNAs: Variety of Roles and Applications in Human Diseases

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 38271

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Special Issue Editor

Prof. Dr. Keun Hur

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Guest Editor

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea
Interests: cancer; metastasis; biomarker; non-coding RNAs; microRNA; lncRNA; exosome

Special Issue Information

Dear Colleagues,

Non-coding RNAs (ncRNAs) are classified as microRNA (miRNA) (containing 19–25 nucleotides) and lncRNA (containing more than 200 nucleotides) according to their length. NcRNAs modulate gene expression at the post-transcriptional level by degradation or translational inhibition of target mRNAs. They are related to many biologic processes, such as development, cell differentiation, proliferation, apoptosis, and inflammation. In addition, ncRNAs are also known to be associated with the diagnosis, classification, progression, and prognosis of many human diseases. Therefore, they can be considered as potential biomarkers for disease diagnosis and as therapeutic targets.

In this Special Issue, we would like to invite submissions of original research articles and review articles focused on ncRNAs, in particular, on their functions, regulatory mechanisms, and applications. We also welcome studies that highlight new technologies, new analysis platforms, new animal models, and new manipulation tools for the study of all kinds of RNA.

Prof. Keun Hur
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Non-coding RNAs
Biomarker
microRNA
lncRNA
Exosome
Cancer
Inflammatory disease
Metabolic disease
Aging

Published Papers (12 papers)

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Research

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14 pages, 4285 KiB

Open AccessArticle

Negative Regulation of ULK1 by microRNA-106a in Autophagy Induced by a Triple Drug Combination in Colorectal Cancer Cells In Vitro

by Rebeca Salgado-García, Jossimar Coronel-Hernández, Izamary Delgado-Waldo, David Cantú de León, Verónica García-Castillo, Eduardo López-Urrutia, Ma. Concepción Gutiérrez-Ruiz, Carlos Pérez-Plasencia and Nadia Jacobo-Herrera

Genes 2021, 12(2), 245; https://doi.org/10.3390/genes12020245 - 9 Feb 2021

Cited by 16 | Viewed by 2969

Abstract

Colorectal cancer (CRC) is among the top three most deadly cancers worldwide. The survival rate for this disease has not been reduced despite the treatments, the reason why the search for therapeutic alternatives continues to be a priority issue in oncology. In this research work, we tested our successful pharmacological combination of three drugs, metformin, doxorubicin, and sodium oxamate (triple therapy, or TT), as an autophagy inducer. Firstly, we employed western blot (WB) assays, where we observed that after 8 h of stimulation with TT, the proteins Unc-51 like autophagy activating kinase 1(ULK1), becline-1, autophagy related 1 protein (Atg4), and LC3 increased in the CRC cell lines HCT116 and SW480 in contrast to monotherapy with doxorubicin. The overexpression of these proteins indicated the beginning of autophagy flow through the activation of ULK1 and the hyperlipidation of LC3 at the beginning of this process. Moreover, we confirm that ULK1 is a bona fide target of hsa-miR-106a-5p (referred to from here on as miR-106a) in HCT116. We also observed through the GFP-LC3 fusion protein that in the presence of miR-106a, the accumulation of autophagy vesicles in cells stimulated with TT is inhibited. These results show that the TT triggered autophagy to modulate miR-106a/ULK1 expression, probably affecting different cellular pathways involved in cellular proliferation, survivance, metabolic maintenance, and cell death. Therefore, considering the importance of autophagy in cancer biology, the study of miRNAs that regulate autophagy in cancer will allow a better understanding of malignant tumors and lead to the development of new disease markers and therapeutic strategies. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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19 pages, 5260 KiB

Open AccessArticle

Long Noncoding RNA HOXA11-AS and Transcription Factor HOXB13 Modulate the Expression of Bone Metastasis-Related Genes in Prostate Cancer

by Aya Misawa, Yukihiro Kondo, Hiroyuki Takei and Toshihiro Takizawa

Genes 2021, 12(2), 182; https://doi.org/10.3390/genes12020182 - 27 Jan 2021

Cited by 17 | Viewed by 3027

Abstract

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression, which play fundamental roles in cancer development. In this study, we found that homeobox A11 antisense RNA (HOXA11-AS), a highly expressed lncRNA in cell lines derived from prostate cancer bone metastases, promoted the cell invasion and proliferation of PC3 prostate cancer cells. Transcription factor homeobox B13 (HOXB13) was identified as an upstream regulator of HOXA11-AS.HOXA11-AS regulated bone metastasis-associated C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor type 2 (CCR2) signaling in both PC3 prostate cancer cells and SaOS2 osteoblastic cells. The HOXB13/HOXA11-AS axis also regulated integrin subunits (ITGAV and ITGB1) specific to prostate cancer bone metastasis. HOXB13, in combination with HOXA11-AS, directly regulated the integrin-binding sialoprotein (IBSP) promoter. Furthermore, conditioned medium containing HOXA11-AS secreted from PC3 cells could induce the expression of CCL2 and IBSP in SaOS2 osteoblastic cells. These results suggest that prostate cancer HOXA11-AS and HOXB13 promote metastasis by regulation of CCL2/CCR2 cytokine and integrin signaling in autocrine and paracrine manners. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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10 pages, 1455 KiB

Open AccessArticle

Predictive Value of Circulating miRNAs in Lymph Node Metastasis for Colon Cancer

by In Hee Lee, Gyeonghwa Kim, Sang Gyu Kwak, Dong Won Baek, Byung Woog Kang, Hye Jin Kim, Su yeon Park, Jun Seok Park, Gyu-Seog Choi, Keun Hur and Jong Gwang Kim

Genes 2021, 12(2), 176; https://doi.org/10.3390/genes12020176 - 27 Jan 2021

Cited by 10 | Viewed by 2192

Abstract

(1) Background: Lymph node (LN) status is an indubitable prognostic factor for survival among colon cancer patients. MicroRNAs (miRNAs) have been implicated in the development and progression of many cancers and are potential biomarkers for cancer diagnosis and prognosis. Therefore, we validated candidate biomarkers using circulating miRNAs by analyzing the plasma miRNA concentrations from patients with colon cancer to predict LN metastasis. (2) Methods: This study included 79 blood samples from patients diagnosed with colon cancer. The NanoString assay was used for screening, and TaqMan miRNA assays for quantitative real-time polymerase chain reaction (RT-PCR) test was used for validation. In a discovery set, we compared the expression of 800 circulating miRNAs in 24 samples (stage 0/I/IIA versus IIIB/IIIC). For validation, a total 79 samples were tested using quantitative RT-PCR. (3) Results: In the discovery set, 10 candidate circulating miRNAs were detected (4 up-regulated miRNAs: miR-323a-3p, miR-382-5p, miR-29a-3p, and miR-376a-3p; 6 down-regulated miRNAs: miR-26a-5p, let-7g-5p, miR-15b-5p, miR-142-3p, miR-374a-5p, and let-7b-5p). In the validation set, higher expression of three circulating miRNAs (miR-323a-3p, miR-382-5p, and miR-376a-3p) was significantly associated with LN metastasis (p = 0.0063, 0.0107, and 0.0022). (4) Conclusions: High expression of circulating miR-323a-3p, miR-382-5p, and miR-376a-3p was significantly associated with LN metastasis in colon cancer patients. These miRNAs could be circulating biomarker candidates that predict the presence of LN metastasis. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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15 pages, 2819 KiB

Open AccessArticle

MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells

by Yeojin Do, Jin Gu Cho, Ji Young Park, Sumin Oh, Doyeon Park, Kyung Hyun Yoo, Myeong-Sok Lee, Byung Su Kwon, Jongmin Kim and Young Yang

Genes 2021, 12(1), 45; https://doi.org/10.3390/genes12010045 - 30 Dec 2020

Cited by 8 | Viewed by 3415

Abstract

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA–mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a–NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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15 pages, 4515 KiB

Open AccessArticle

MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells

by Dansaem Lim, Jin Gu Cho, Eunsik Yun, Aram Lee, Hong-Yeoul Ryu, Young Joo Lee, Sukjoon Yoon, Woochul Chang, Myeong-Sok Lee, Byung Su Kwon and Jongmin Kim

Genes 2021, 12(1), 9; https://doi.org/10.3390/genes12010009 - 23 Dec 2020

Cited by 16 | Viewed by 3015

Abstract

Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial–mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a–AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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11 pages, 271 KiB

Open AccessArticle

Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis

by Vytenis Petkevicius, Greta Streleckiene, Kotryna Balciute, Alexander Link, Marcis Leja, Peter Malfertheiner, Jurgita Skieceviciene and Juozas Kupcinskas

Genes 2020, 11(12), 1505; https://doi.org/10.3390/genes11121505 - 15 Dec 2020

Cited by 18 | Viewed by 2090

Abstract

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of MALAT1 rs3200401 CT genotype had the significantly higher odds of atrophic gastritis than those with CC genotype (OR-1.81; 95% CI 1.17–2.80, p = 0.0066). Higher odds of AG were found in a recessive model (CC vs. TT + CT) for ANRIL rs1333045 (OR-1.88; 95% CI 1.19–2.95, p = 0.0066). Carriers of ANRIL (rs17694493) GG genotype had higher odds of gastric cancer (OR-4.93; 95% CI 1.28–19.00) and atrophic gastritis (OR-5.11; 95% CI 1.10–23.80) compared with the CC genotype, and carriers of HOTAIR rs17840857 TG genotype had higher odds of atrophic gastritis (OR-1.61 95% CI 1.04–2.50) compared with the TT genotype; however, the ORs did not reach the adjusted significance threshold (p < 0.007). In summary, our data provide novel evidence for a possible link between lncRNA SNPs and premalignant condition of gastric cancer, suggesting the involvement of lncRNAs in gastric cancer development. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

10 pages, 705 KiB

Open AccessArticle

Transfer-RNA-Derived Fragments Are Potential Prognostic Factors in Patients with Squamous Cell Carcinoma of the Head and Neck

by Xiaolian Gu, Lixiao Wang, Philip J. Coates, Linda Boldrup, Robin Fåhraeus, Torben Wilms, Nicola Sgaramella and Karin Nylander

Genes 2020, 11(11), 1344; https://doi.org/10.3390/genes11111344 - 13 Nov 2020

Cited by 16 | Viewed by 1984

Abstract

Transfer-RNA-derived fragments (tRFs) are a class of small non-coding RNAs that are functionally different from their parental transfer RNAs (tRNAs). tRFs can regulate gene expression by several mechanisms, and are involved in a variety of pathological processes. Here, we aimed at understanding the composition and abundance of tRFs in squamous cell carcinoma of the head and neck (SCCHN), and evaluated the potential of tRFs as prognostic markers in this cancer type. We obtained tRF expression data from The Cancer Genome Atlas (TCGA) HNSC cohort (523 patients) using MINTbase v2.0, and correlated to available TCGA clinical data. RNA-binding proteins were predicted according to the calculated Position Weight Matrix (PWM) score from the RNA-Binding Protein DataBase (RBPDB). A total of 10,158 tRFs were retrieved and a high diversity in expression levels was seen. Fifteen tRFs were found to be significantly associated with overall survival (Kaplan-Meier survival analysis, log rank test p-value < 0.01). The top prognostic marker, tRF-20-S998LO9D (p < 0.001), was further measured in tumor and tumor-free samples from 16 patients with squamous cell carcinoma of the oral tongue and 12 healthy controls, and was significantly upregulated in tumor compared to matched tumor-free tongue (p < 0.001). Results suggest that tRFs are useful prognostic markers in SCCHN. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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17 pages, 2840 KiB

Open AccessArticle

Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer

by Gabriela Figueroa-González, José F. Carrillo-Hernández, Itzel Perez-Rodriguez, David Cantú de León, Alma D. Campos-Parra, Antonio D. Martínez-Gutiérrez, Jossimar Coronel-Hernández, Verónica García-Castillo, César López-Camarillo, Oscar Peralta-Zaragoza, Nadia J. Jacobo-Herrera, Mariano Guardado-Estrada and Carlos Pérez-Plasencia

Genes 2020, 11(9), 1058; https://doi.org/10.3390/genes11091058 - 8 Sep 2020

Cited by 10 | Viewed by 3652

Abstract

Background: Serine Threonine Kinase 11 (STK11), also known as LKB1, is a tumor suppressor gene that regulates several biological processes such as apoptosis, energetic metabolism, proliferation, invasion, and migration. During malignant progression, different types of cancer inhibit STK11 function by mutation or epigenetic inactivation. In Head and Neck Cancer, it is unclear what mechanism is involved in decreasing STK11 levels. Thus, the present work aims to determine whether STK11 expression might be regulated through epigenetic or post-translational mechanisms. Methods: Expression levels and methylation status for STK11 were analyzed in 59 cases of head and neck cancer and 10 healthy tissue counterparts. Afterward, we sought to identify candidate miRNAs exerting post-transcriptional regulation of STK11. Then, we assessed a luciferase gene reporter assay to know if miRNAs directly target STK11 mRNA. The expression levels of the clinical significance of mir-100-3p, -5p, and STK11 in 495 HNC specimens obtained from the TCGA database were further analyzed. Finally, the Kaplan–Meier method was used to estimate the prognostic significance of the miRNAs for Overall Survival, and survival curves were compared through the log-rank test. Results: STK11 was under-expressed, and its promoter region was demethylated or partially methylated. miR-17-5p, miR-106a-5p, miR-100-3p, and miR-100-5p could be negative regulators of STK11. Our experimental data suggested evidence that miR-100-3p and -5p were over-expressed in analyzed tumor patient samples. Luciferase gene reporter assay experiments showed that miR-100-3p targets and down-regulates STK11 mRNA directly. With respect to overall survival, STK11 expression level was significant for predicting clinical outcomes. Conclusion: This is, to our knowledge, the first report of miR-100-3p targeting STK11 in HNC. Together, these findings may support the importance of regulation of STK11 through post-transcriptional regulation in HNC and the possible contribution to the carcinogenesis process in this neoplasia. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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10 pages, 1722 KiB

Open AccessArticle

Expression of the Long Noncoding RNA GAS5 Correlates with Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

by Man-Hoon Han, Jee Hyun Lee, Gyeonghwa Kim, Eunhye Lee, Yu Rim Lee, Se Young Jang, Hye Won Lee, Jae Min Chun, Young Seok Han, Jun Sik Yoon, Min Kyu Kang, Won Kee Lee, Young Oh Kweon, Won Young Tak, Soo Young Park, Jung Gil Park and Keun Hur

Genes 2020, 11(5), 545; https://doi.org/10.3390/genes11050545 - 13 May 2020

Cited by 30 | Viewed by 2564

Abstract

Background: Advanced liver fibrosis is the most important prognostic factor in nonalcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA), growth arrest-specific transcript 5 (GAS5), is associated with the inhibition of liver fibrogenesis, and its levels are decreased in cirrhotic liver. Methods: We analyzed 51 patients with NAFLD, the diagnosis of which was confirmed by liver biopsy. Expression of GAS5 in both the liver and plasma of the patients was analyzed using a quantitative real-time polymerase chain reaction according to the fibrosis stage. Results: Plasma GAS5 expression was significantly higher in patients with advanced fibrosis than in those without. As the fibrosis progressed, GAS5 expression in plasma increased, with the exception of that in cirrhotic livers. Plasma levels of GAS5 were lower in patients with cirrhosis than in those with advanced fibrosis. Conclusion: Elevated circulating levels of the lncRNA GAS5 are associated with the progression of liver fibrosis prior to the development of cirrhosis. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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11 pages, 2662 KiB

Open AccessArticle

MicroRNA-1258 Inhibits the Proliferation and Migration of Human Colorectal Cancer Cells through Suppressing CKS1B Expression

by Jin-Seong Hwang, Eun-Jeong Jeong, Jinhyeon Choi, Yeo-Jin Lee, Eunsun Jung, Seon-Kyu Kim, Jeong-Ki Min, Tae-Su Han and Jang-Seong Kim

Genes 2019, 10(11), 912; https://doi.org/10.3390/genes10110912 - 8 Nov 2019

Cited by 25 | Viewed by 3047

Abstract

Increasing evidence has demonstrated that increased expression of cyclin-dependent kinase regulatory subunit 1B (CKS1B) is associated with the pathogenesis of many human cancers, including colorectal cancer (CRC). However, the regulatory mechanisms underlying the expression of CKS1B in CRC are not completely understood. Here, we investigate the role played by microRNAs in the expression of CKS1B and carcinogenesis in CRC. Among the six microRNAs predicted to target CKS1B gene expression, only miR-1258 was revealed to downregulate CKS1B expression through binding to its 3’-UTR region, as ectopic miR-1258 expression suppressed CKS1B expression and vice versa. In CRC, miR-1258 expression also decreased cell proliferation and migration in vitro and tumor growth in vivo, similar to cells with silenced CKS1B expression. Considering the highly increased levels of CKS1B and decreased expression of miR-1258 in tumors from CRC patients, these findings suggest that miR-1258 may play tumor-suppressive roles by targeting CKS1B expression in CRC. However, the therapeutic significance of these findings should be evaluated in clinical settings. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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Review

Jump to: Research

17 pages, 1335 KiB

Open AccessReview

MicroRNAs Regulate Intestinal Immunity and Gut Microbiota for Gastrointestinal Health: A Comprehensive Review

by Kefan Bi, Xujun Zhang, Wenbiao Chen and Hongyan Diao

Genes 2020, 11(9), 1075; https://doi.org/10.3390/genes11091075 - 12 Sep 2020

Cited by 38 | Viewed by 6537

Abstract

MicroRNAs are small non-coding RNAs regulating gene expression at the post-transcriptional level. The regulation of microRNA expression in the gut intestine is gradually recognized as one of the crucial contributors of intestinal homeostasis and overall health. Recent studies indicated that both the microRNAs endogenous in the gut intestine and exogenous from diets could play influential roles in modulating microbial colonization and intestinal immunity. In this review, we discuss the biological functions of microRNAs in regulating intestinal homeostasis by modulating intestinal immune responses and gut microbiota. We particularly focus on addressing the microRNA-dependent communication and interactions among microRNA, gut microbiota, and intestinal immune system. Besides, we also summarize the roles of diet-derived microRNAs in host-microbiome homeostasis and their benefits on intestinal health. A better understanding of the relationships among intestinal disorders, microRNAs, and other factors influencing intestinal health can facilitate the application of microRNA-based therapeutics for gastrointestinal diseases. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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13 pages, 736 KiB

Open AccessReview

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

by Hyun-Soo Cho, Tae-Su Han, Keun Hur and Hyun Seung Ban

Genes 2019, 10(12), 1008; https://doi.org/10.3390/genes10121008 - 4 Dec 2019

Cited by 15 | Viewed by 2823

Abstract

Hypoxia-inducible factors (HIFs) are transcription factors that play central roles in cellular responses against hypoxia. In most cancers, HIFs are closely associated with tumorigenesis by regulating cell survival, angiogenesis, metastasis, and adaptation to the hypoxic tumor microenvironment. Recently, non-coding RNAs (ncRNAs) have been reported to play critical roles in the hypoxic response in various cancers. Here, we review the roles of hypoxia-response ncRNAs in gastrointestinal cancer, with a particular focus on microRNAs and long ncRNAs, and discuss the functional relationships and regulatory mechanisms between HIFs and ncRNAs. Full article

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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