Molecular Mechanisms and Clinical Implications of Non-coding RNAs in Cancer

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (20 November 2023) | Viewed by 11271

Special Issue Editors


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Guest Editor
Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
Interests: novel biomarkers of human gastrointestinal cancers; ncRNAs; circRNAs; lncRNAs; miRNAs; treatment of cancer; treatment of infectious diseases

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Guest Editor
Nutritional Sciences Division, School of Medicine, King’s College London, London, UK
Interests: intestinal sugar transport; nutrient sensing; vitamin C; polyphenolics; diabetes; obesity
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Special Issue Information

Dear Colleagues, 

Non-coding RNAs (ncRNAs) arise from genomic regions without protein-coding potential and include abundant and functional types such as small nuclear RNAs (snRMAs), small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). NcRNAs display a variety of mechanisms and functions by regulating gene expression at the levels of transcription, RNA processing and translation, and participating in virtually all cellular processes. Dysregulated ncRNAs are involved in many complex human diseases and exert distinct functions like oncogenic and tumor suppressive roles. Circulating ncRNAs have already shown potentials as diagnostic and prognostic biomarkers in various cancers. However, a few functions of ncRNAs need be characterized.

Aims: In this proposal, it will be examined that several ncRNAs contribute significantly to pathogenesis, oncogenesis, tumor suppression and cell cycle arrest of diverse cancer types and also give a summary of the pathways, which would be of necessity to further investigate the diverse gene regulatory mechanisms of ncRNAs, to unveil the complicated gene regulatory network involving ncRNAs, and ultimately provide novel strategies for cancer diagnosis and therapy. The different perspectives on the distinct functions, regulatory mechanisms and potentials clinic application of ncRNAs will be discussed in this proposal.

The scope for the Special Issue: As a small ncRNA, miRNA is that functions in RNA silencing and post-transcriptional regulation of gene expression via base-pairing with complementary sequences within mRNA and cleaving or destabilizing it. LncRNA can affect many cellular processes, such as cell cycle, survival, migration and metabolism, and correlate with malignancies in lung, breast, liver, bladder, and prostate cancer. circRNAs function in co-/post-transcriptional regulation by competing with linear splicing of the host mRNA or sponging for miRNAs, and thus show potentials in gene silencing and RNA interference, which provides a novel approach in cancer treatment. We hope to attract review articles and original research which describe the current state of ncRNAs in cancer. Papers are published upon acceptance, regardless of the Special Issue publication date.

Potential topics include but are not limited to the following: ncRNAs in cancer including miRNAs, lncRNAs and circRNAs.

  • Non-coding RNAs (ncRNAs) have emerged as one important kind of molecules that can regulate altered genes contributing;
  • Characterization of ncRNAs and their potential functions;
  • NcRNA can affect many cellular processes, such as cell cycle, survival, migration and metabolism;
  • Identification and characterization of microRNAs in cancer;
  • Identification and characterization of lncRNAs in cancer;
  • Identification and characterization of circRNAs in cancer;
  • New strategies and efforts to identify ncRNA (miRNAs, lncRNA and circRNAs);
  • Clinical Implications of Non-coding RNAs in Cancer.

Prof. Dr. Jin Wang
Dr. Christopher Corpe
Guest Editors

Manuscript Submission Information

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Keywords

  • non-coding RNA
  • cancer
  • regulatory mechanism
  • clinical implications

Published Papers (6 papers)

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Research

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20 pages, 4106 KiB  
Article
Possible Involvement of Long Non-Coding RNAs GNAS-AS1 and MIR205HG in the Modulation of 5-Fluorouracil Chemosensitivity in Colon Cancer Cells through Increased Extracellular Release of Exosomes
by Shamin Azwar, Chin Tat Ng, Siti Yazmin Zahari Sham, Heng Fong Seow, Minhian Chai, Mohd Faizal Ghazali and Mohd Faisal Jabar
Non-Coding RNA 2024, 10(2), 25; https://doi.org/10.3390/ncrna10020025 - 15 Apr 2024
Viewed by 311
Abstract
A growing number of studies have suggested the involvement of long non-coding RNAs as the key players in not just the initiation and progression of the tumor microenvironment, but also in chemotherapy tolerance. In the present study, generated 5-FU-resistant SW480/DR cells were analyzed [...] Read more.
A growing number of studies have suggested the involvement of long non-coding RNAs as the key players in not just the initiation and progression of the tumor microenvironment, but also in chemotherapy tolerance. In the present study, generated 5-FU-resistant SW480/DR cells were analyzed via cDNA microarray for its aberrant lncRNAs and mRNAs expression in comparison with the 5-FU-susceptible SW480/DS cells. Among the 126 lncRNAs described, lncRNAs GNAS-AS1, MIR205HG, and LOC102723721 have been identified to be significantly upregulated, while lncRNs lnc-RP11-597K23.2.1-2, LOC100507639, and CCDC144NL-AS1 have been found to be significantly downregulated. In the meantime, bioinformatic analysis through gene ontology studies of aberrantly expressed mRNAs revealed “regulated exocytosis”, among others, as the biological process most impacted in SW480/DR cells. To investigate, exosome purification was then carried out and its characterization were validated via transmission electron microscopy and nanoparticle tracking analysis. Interestingly, it was determined that the 5-FU-resistant SW480/DR cells secretes significantly higher concentration of extracellular vesicles, particularly, exosomes when compared to the 5-FU-susceptible SW480/DS cells. Based on the lncRNA-mRNA interaction network analysis generated, lncRNA GNAS-AS1 and MIR205HG have been identified to be potentially involved in the incidence of 5-FU resistance in SW480 colon cancer cells through promoting increased release of exosomes into the intercellular matrix. Our study hopes not only to provide insights on the list of involved candidate lncRNAs, but also to elucidate the role exosomes play in the initiation and development of 5-FU chemotherapy resistance in colon cancer cells. Full article
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24 pages, 4105 KiB  
Article
MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B
by Katharina Jonas, Felix Prinz, Manuela Ferracin, Katarina Krajina, Alexander Deutsch, Tobias Madl, Beate Rinner, Ondrej Slaby, Christiane Klec and Martin Pichler
Non-Coding RNA 2024, 10(1), 2; https://doi.org/10.3390/ncrna10010002 - 26 Dec 2023
Viewed by 1696
Abstract
MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still [...] Read more.
MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC). Therefore, we aimed to characterize a novel miRNA with a potential role in TNBC. Based on a previous study, we selected miR-4646-5p, a miRNA with a still unknown function in breast cancer. We discovered that higher expression of miR-4646-5p in TNBC patients is associated with better survival. In vitro assays showed that miR-4646-5p overexpression reduces growth, proliferation, and migration of TNBC cell lines, whereas inhibition had the opposite effect. Furthermore, we found that miR-4646-5p inhibits the tube formation ability of endothelial cells, which may indicate anti-angiogenic properties. By whole transcriptome analysis, we not only observed that miR-4646-5p downregulates many oncogenic factors, like tumor-promoting cytokines and migration- and invasion-related genes, but were also able to identify a direct target, the GRAM domain-containing protein 1B (GRAMD1B). GRAMD1B is involved in cellular cholesterol transport and its knockdown phenocopied the growth-reducing effects of miR-4646-5p. We thus conclude that GRAMD1B may partly contribute to the diverse tumor-suppressive effects of miR-4646-5p in TNBC. Full article
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16 pages, 3000 KiB  
Article
Discovery of Novel miRNAs in Colorectal Cancer: Potential Biological Roles and Clinical Utility
by Iael Weissberg Minutentag, Ana Laura Seneda, Mateus C. Barros-Filhos, Márcio de Carvalho, Vanessa G. P. Souza, Claudia N. Hasimoto, Marcelo P. T. Moraes, Fabio A. Marchi, Wan L. Lam, Patricia P. Reis and Sandra A. Drigo
Non-Coding RNA 2023, 9(6), 65; https://doi.org/10.3390/ncrna9060065 - 26 Oct 2023
Viewed by 1723
Abstract
Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO [...] Read more.
Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO data (discovery and validation groups). We used TCGA data from five tissues to analyze miRNA tissue specificity. miRDB was used to predict miRNA targets, and the UCSC Xena Browser was used to evaluate target expression. After successive analyses, we identified 15 novel miRNAs with the same expression patterns in CRC in both the discovery and validation groups. Four molecules (nov-miR-13844-5p, nov-miR-7154-5p, nov-miR-5035-3p, and nov-miR-590-5p) were differentially expressed in proximal and distal CRC. The nov-miR-3345-5p and nov-miR-13172-3p, which are upregulated in tumors, are only expressed in colorectal tissues. These molecules have been linked to a worse prognosis in right-sided colon and rectal carcinomas. An analysis revealed an association between eight novel miRNAs and 81 targets, mostly cancer-related genes, with varying expression based on tumor location. These findings provide new miRNAs with potential biological relevance, molecular biomarkers, and therapeutic targets for CRC treatment. Full article
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14 pages, 1790 KiB  
Communication
Structural Modifications and Novel Protein-Binding Sites in Pre-miR-675—Explaining Its Regulatory Mechanism in Carcinogenesis
by Abhishek Dey
Non-Coding RNA 2023, 9(4), 45; https://doi.org/10.3390/ncrna9040045 - 10 Aug 2023
Viewed by 2172
Abstract
Pre-miR-675 is a microRNA expressed from the exon 1 of H19 long noncoding RNA, and the atypical expression of pre-miR-675 has been linked with several diseases and disorders including cancer. To execute its function inside the cell, pre-miR-675 is folded into a particular [...] Read more.
Pre-miR-675 is a microRNA expressed from the exon 1 of H19 long noncoding RNA, and the atypical expression of pre-miR-675 has been linked with several diseases and disorders including cancer. To execute its function inside the cell, pre-miR-675 is folded into a particular conformation, which aids in its interaction with several other biological molecules. However, the exact folding dynamics of pre-miR-675 and its protein-binding motifs are currently unknown. Moreover, how H19 lncRNA and pre-miR-675 crosstalk and modulate each other’s activities is also unclear. The detailed structural analysis of pre-miR-675 in this study determines its earlier unknown conformation and identifies novel protein-binding sites on pre-miR-675, thus making it an excellent therapeutic target against cancer. Co-folding analysis between H19 lncRNA and pre-miR-675 determine structural transformations in pre-miR-675, thus describing the earlier unknown mechanism of interaction between these two molecules. Comprehensively, this study details the conformation of pre-miR-675 and its protein-binding sites and explains its relationship with H19 lncRNA, which can be interpreted to understand the role of pre-miR-675 in the development and progression of tumorigenesis and designing new therapeutics against cancers. Full article
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Review

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24 pages, 1753 KiB  
Review
Crosstalk between Non-Coding RNAs and Wnt/β-Catenin Signaling in Head and Neck Cancer: Identification of Novel Biomarkers and Therapeutic Agents
by Anjana Sajeev, Bandari BharathwajChetty, Ravichandran Vishwa, Mohammed S. Alqahtani, Mohamed Abbas, Gautam Sethi and Ajaikumar B. Kunnumakkara
Non-Coding RNA 2023, 9(5), 63; https://doi.org/10.3390/ncrna9050063 - 17 Oct 2023
Viewed by 1745
Abstract
Head and neck cancers (HNC) encompass a broad spectrum of neoplastic disorders characterized by significant morbidity and mortality. While contemporary therapeutic interventions offer promise, challenges persist due to tumor recurrence and metastasis. Central to HNC pathogenesis is the aberration in numerous signaling cascades. [...] Read more.
Head and neck cancers (HNC) encompass a broad spectrum of neoplastic disorders characterized by significant morbidity and mortality. While contemporary therapeutic interventions offer promise, challenges persist due to tumor recurrence and metastasis. Central to HNC pathogenesis is the aberration in numerous signaling cascades. Prominently, the Wnt signaling pathway has been critically implicated in the etiology of HNC, as supported by a plethora of research. Equally important, variations in the expression of non-coding RNAs (ncRNAs) have been identified to modulate key cancer phenotypes such as cellular proliferation, epithelial-mesenchymal transition, metastatic potential, recurrence, and treatment resistance. This review aims to provide an exhaustive insight into the multifaceted influence of ncRNAs on HNC, with specific emphasis on their interactions with the Wnt/β-catenin (WBC) signaling axis. We further delineate the effect of ncRNAs in either exacerbating or attenuating HNC progression via interference with WBC signaling. An overview of the mechanisms underlying the interplay between ncRNAs and WBC signaling is also presented. In addition, we described the potential of various ncRNAs in enhancing the efficacy of chemotherapeutic and radiotherapeutic modalities. In summary, this assessment posits the potential of ncRNAs as therapeutic agents targeting the WBC signaling pathway in HNC management. Full article
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22 pages, 1674 KiB  
Review
Functional Relevance of the Long Intergenic Non-Coding RNA Regulator of Reprogramming (Linc-ROR) in Cancer Proliferation, Metastasis, and Drug Resistance
by José A. Peña-Flores, Diego Enríquez-Espinoza, Daniela Muela-Campos, Alexis Álvarez-Ramírez, Angel Sáenz, Andrés A. Barraza-Gómez, Kenia Bravo, Marvin E. Estrada-Macías and Karla González-Alvarado
Non-Coding RNA 2023, 9(1), 12; https://doi.org/10.3390/ncrna9010012 - 31 Jan 2023
Cited by 3 | Viewed by 2830
Abstract
Cancer is responsible for more than 10 million deaths every year. Metastasis and drug resistance lead to a poor survival rate and are a major therapeutic challenge. Substantial evidence demonstrates that an increasing number of long non-coding RNAs are dysregulated in cancer, including [...] Read more.
Cancer is responsible for more than 10 million deaths every year. Metastasis and drug resistance lead to a poor survival rate and are a major therapeutic challenge. Substantial evidence demonstrates that an increasing number of long non-coding RNAs are dysregulated in cancer, including the long intergenic non-coding RNA, regulator of reprogramming (linc-ROR), which mostly exerts its role as an onco-lncRNA acting as a competing endogenous RNA that sequesters micro RNAs. Although the properties of linc-ROR in relation to some cancers have been reviewed in the past, active research appends evidence constantly to a better comprehension of the role of linc-ROR in different stages of cancer. Moreover, the molecular details and some recent papers have been omitted or partially reported, thus the importance of this review aimed to contribute to the up-to-date understanding of linc-ROR and its implication in cancer tumorigenesis, progression, metastasis, and chemoresistance. As the involvement of linc-ROR in cancer is elucidated, an improvement in diagnostic and prognostic tools could promote and advance in targeted and specific therapies in precision oncology. Full article
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