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Functional and Structural Insights of Non-coding RNA in Cancer

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (16 June 2023) | Viewed by 8965

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Special Issue Editors

Dr. Guillermo Barreto

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Guest Editor

CNRS, Laboratoire IMoPA, Université de Lorraine, UMR 7365, F-54000 Nancy, France
Interests: lung cancer; epigenetics; transcription; ncRNA; histone modifications; DNA methylation

Dr. Marco Marcia

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Guest Editor

European Molecular Biology Laboratory (EMBL) Grenoble, Grenoble, France
Interests: long non-coding RNAs; epigenetics; splicing; RNA structure

Dr. Bruno Charpentier

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Guest Editor

CNRS, Laboratoire IMoPA, Université de Lorraine, UMR 7365, F-54000 Nancy, France
Interests: structure-function relationship of ribonucleoproteins and their biogenesis

Special Issue Information

Dear Colleagues,

The majority of the eukaryotic genome is transcribed into non-coding RNAs (ncRNAs) that are not translated into proteins, and include small non-coding RNAs and long non-coding RNAs. Increasing evidence demonstrates that ncRNAs play key roles in different cellular processes in the cell nucleus, the cytosol, and the extracellular space. NcRNAs frequently elicit their functions as components of RNA–protein complexes (ribonucleoproteins, RNPs) that act in response to a broad spectrum of molecular mechanisms. Different ncRNA biotypes have been reported to be dysregulated in various cancer types, thereby opening diagnostic and therapeutic possibilities in cancer involving ncRNAs. This Special Issue aims to publish research articles elucidating functional and structural aspects of the molecular mechanisms involving ncRNAs during the tumorigenesis and metastasis of different cancer types.

Dr. Guillermo Barreto
Dr. Marco Marcia
Dr. Bruno Charpentier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

ncRNA
lncRNA
RNPs
cancer
epigenetics
structural biology
transcription
splicing
RNA structure

Published Papers (6 papers)

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Research

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21 pages, 5626 KiB

Open AccessArticle

ncRNAs Orchestrate Chemosensitivity Induction by Neddylation Blockades

by Andrea Pérez-González, Ivonne Ramírez-Díaz, Josué Guzmán-Linares, Pouya Sarvari, Pourya Sarvari and Karla Rubio

Cancers 2024, 16(4), 825; https://doi.org/10.3390/cancers16040825 - 18 Feb 2024

Viewed by 1360

Abstract

We performed an integrative transcriptomic in silico analysis using lung adenocarcinoma A549 cells treated with the neddylation inhibitor MLN4924 and the gefitinib-resistant PC9 cell line (PC9GR). We focused on the transcriptional effects of the top differentially expressed ncRNA biotypes and their correlating stemness factors. Interestingly, MLN4924-treated cells showed a significant upregulation of mRNAs involved in carcinogenesis, cell attachment, and differentiation pathways, as well as a parallel downregulation of stemness maintenance and survival signaling pathways, an effect that was inversely observed in PC9GR cells. Moreover, we found that stemness factor expression could be contrasted by selected up-regulated ncRNAs upon MLN4924 treatment in a dose and time-independent manner. Furthermore, upregulated miRNAs and lncRNA-targeted mRNAs showed an evident enrichment of proliferation, differentiation, and apoptosis pathways, while downregulated ncRNA-targeted mRNAs were implicated in stem cell maintenance. Finally, our results proved that stemness (KLF4 and FGFR2) and epithelial–mesenchymal transition (ZEB2, TWIST2, SNAI2, CDH2, and VIM) factors, which are highly expressed in PC9GR cells compared to gefitinib-sensitive PC9 cells, could be abrogated with the neddylation inhibitor MLN4924 mainly through activation of epithelial differentiation pathways, thus exerting a protective role in lung cancer cells and chemosensitivity against lung tumorigenic transformation. Full article

(This article belongs to the Special Issue Functional and Structural Insights of Non-coding RNA in Cancer)

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20 pages, 2157 KiB

Open AccessArticle

Adenosine Methylation Level of miR-125a-5p Promotes Anti-PD-1 Therapy Escape through the Regulation of IGSF11/VSIG3 Expression

by Gwenola Bougras-Cartron, Arulraj Nadaradjane, Marie-Pierre Joalland, Lisenn Lalier-Bretaudeau, Judith Raimbourg and Pierre-François Cartron

Cancers 2023, 15(12), 3188; https://doi.org/10.3390/cancers15123188 - 14 Jun 2023

Viewed by 1298

Abstract

Background: Despite encouraging anti-tumour activity in lung cancer, anti-PD-1 therapy has encountered increasing resistance to treatment. Several companion diagnostic assays have been performed to identify patients who may benefit from this immunotherapy and to adapt this therapy in case of acquired resistance. Methods: A large panel of methods was used for the analysis of expression and methylation levels of miRNAs (qPCR, MemiRIP, …), protein/miRNA interactions (CLIP, oligo pull-down, …), and protein–protein interactions (CoIP) in cells and/or blood samples. Results: Our work highlights that the saturation of PD-1 by anti-PD1 therapies induces an immune escape phenomenon due to the overexpression of IGSF11 following adenosine methylation of miR-125a-5p. Mechanistically, we identify METTL3/KHDRBS3 and HuR as two crucial players in the methylation and the loss of the repressive function of this miRNA. Finally, our work shows that the adenosine methylation of miR-125a-5p is analyzable from EVs/exosomes from longitudinal blood samples and that such EVs/exosomes modulate the IGSF11/VSIG3 expression in lung cancer cells to promote an immune escape phenomenon. Conclusions: Our data provide a biomarker (m6A-miR-125a-5p level) and two therapeutic solutions (anti-IGSF11 antibody and METTL3 inhibitor) that could potentially address the anti-PD1 therapy failure in the context of precision and personalized medicine. Full article

(This article belongs to the Special Issue Functional and Structural Insights of Non-coding RNA in Cancer)

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Review

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22 pages, 2018 KiB

Open AccessReview

Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS

by Guruprasadh Swaminathan, Diana G. Rogel-Ayala, Amine Armich and Guillermo Barreto

Cancers 2024, 16(5), 868; https://doi.org/10.3390/cancers16050868 - 21 Feb 2024

Viewed by 1074

Abstract

The eukaryotic genome is mainly transcribed into non-coding RNAs (ncRNAs), including different RNA biotypes, such as micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), among others. Although miRNAs are assumed to act primarily in the cytosol, mature miRNAs have been reported and functionally characterized in the nuclei of different cells. Further, lncRNAs are important regulators of different biological processes in the cell nucleus as part of different ribonucleoprotein complexes. CircRNAs constitute a relatively less-characterized RNA biotype that has a circular structure as result of a back-splicing process. However, circRNAs have recently attracted attention in different scientific fields due to their involvement in various biological processes and pathologies. In this review, we will summarize recent studies that link to cancer miRNAs that have been functionally characterized in the cell nucleus, as well as lncRNAs and circRNAs that are bound by core components of the polycomb repressive complex 2 (PRC2) or the protein fused in sarcoma (FUS), highlighting mechanistic aspects and their diagnostic and therapeutic potential. Full article

(This article belongs to the Special Issue Functional and Structural Insights of Non-coding RNA in Cancer)

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32 pages, 1276 KiB

Open AccessReview

The Long Non-Coding RNA ANRIL in Cancers

by Aymeric Sanchez, Julien Lhuillier, Guillaume Grosjean, Lilia Ayadi and Sylvain Maenner

Cancers 2023, 15(16), 4160; https://doi.org/10.3390/cancers15164160 - 17 Aug 2023

Cited by 2 | Viewed by 2033

Abstract

ANRIL (Antisense Noncoding RNA in the INK4 Locus), a long non-coding RNA encoded in the human chromosome 9p21 region, is a critical factor for regulating gene expression by interacting with multiple proteins and miRNAs. It has been found to play important roles in various cellular processes, including cell cycle control and proliferation. Dysregulation of ANRIL has been associated with several diseases like cancers and cardiovascular diseases, for instance. Understanding the oncogenic role of ANRIL and its potential as a diagnostic and prognostic biomarker in cancer is crucial. This review provides insights into the regulatory mechanisms and oncogenic significance of the 9p21 locus and ANRIL in cancer. Full article

(This article belongs to the Special Issue Functional and Structural Insights of Non-coding RNA in Cancer)

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17 pages, 2090 KiB

Open AccessReview

Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models

by Ubaidilla M. Datkhayev, Venera Rakhmetova, Abay M. Shepetov, Almat Kodasbayev, Gulmira Makhanbetovna Datkayeva, Sabit B. Pazilov and Ammad Ahmad Farooqi

Cancers 2023, 15(15), 3971; https://doi.org/10.3390/cancers15153971 - 4 Aug 2023

Cited by 1 | Viewed by 1072

Abstract

Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the “ubiquitinome” is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis. Full article

(This article belongs to the Special Issue Functional and Structural Insights of Non-coding RNA in Cancer)

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33 pages, 3630 KiB

Open AccessReview

Insights into the Role of LncRNAs and miRNAs in Glioma Progression and Their Potential as Novel Therapeutic Targets

by Mateusz Kciuk, Esam Bashir Yahya, Montaha Mohamed Ibrahim Mohamed, Muhanad A. Abdulsamad, Abdulmutalib A. Allaq, Adrianna Gielecińska and Renata Kontek

Cancers 2023, 15(13), 3298; https://doi.org/10.3390/cancers15133298 - 22 Jun 2023

Cited by 4 | Viewed by 1486

Abstract

Accumulating evidence supports that both long non-coding and micro RNAs (lncRNAs and miRNAs) are implicated in glioma tumorigenesis and progression. Poor outcome of gliomas has been linked to late-stage diagnosis and mostly ineffectiveness of conventional treatment due to low knowledge about the early stage of gliomas, which are not possible to observe with conventional diagnostic approaches. The past few years witnessed a revolutionary advance in biotechnology and neuroscience with the understanding of tumor-related molecules, including non-coding RNAs that are involved in the angiogenesis and progression of glioma cells and thus are used as prognostic biomarkers as well as novel therapeutic targets. The emerging research on lncRNAs and miRNAs highlights their crucial role in glioma progression, offering new insights into the disease. These non-coding RNAs hold significant potential as novel therapeutic targets, paving the way for innovative treatment approaches against glioma. This review encompasses a comprehensive discussion about the role of lncRNAs and miRNAs in gene regulation that is responsible for the promotion or the inhibition of glioma progression and collects the existing links between these key cancer-related molecules. Full article

(This article belongs to the Special Issue Functional and Structural Insights of Non-coding RNA in Cancer)

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