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Targeting Cancer through RNA Biology 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 11853

Special Issue Editor


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Guest Editor
Faculty of Health and Applied Sciences, University of the West of England, Bristol BS16 1QY, UK
Interests: RNA biology; RNA binding proteins; alternative splicing; splice factors; splice factor kinases; mRNA translation; microRNAs
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Special Issue Information

Dear Colleagues,

Over the last four decades, the field of molecular biology has expanded at an incredible rate, to the extent that it is a real challenge to keep up with new developments. Specific areas of interest have emerged and grown, namely genomics, epigenetics, cell signalling, cell biology, and RNA biology, to name but a few. What do we mean by RNA biology? It is a complex mixture of topics; the versatile nature of RNA structure, ribozymes, RNA-binding proteins, and a huge assortment of co- and post-transcriptional processes that help to regulate gene expression. In the cell nucleus, we contend with alternative polyadenylation sites, RNA editing, alternative splicing, regulated RNA export, and epigenetic processes in which RNA molecules play a key part; and in the cytoplasm, mRNA localisation, regulated mRNA translation, and mRNA stability. As if that were not enough, we also have to consider a myriad of noncoding RNAs, both long and short. Noncoding RNAs are involved in epigenetic regulation and cis-regulation of pre-mRNA splicing, mRNA translation and decay. All of these processes contribute immensely to the regulation of gene expression in development and disease. Of particular note is that over 94% of human genes are alternatively spliced, and one in six disease-associated mutations perturb pre-mRNA splicing.

Given these layers of complexity, it is not surprising to find that RNA biology can and does go wrong in cancer. There is increasing interest in looking at RNA biomarkers, notably the presence of specific cancer-associated microRNAs in the blood or urine. The expression of splice factors and the alternative splicing of key cancer-associated genes is frequently altered. Therefore, a growing assortment of novel anticancer strategies that target RNA-mediated processes are being developed. These include the manipulation of alternative splicing through oligonucleotides and splice factor kinase inhibitors and the manipulation of mRNA translation and nonsense-mediated decay. The purpose of this Special Issue is to draw attention to the significant new possibilities that RNA biology offers in the fight against cancer.

Dr. Michael Ladomery
Guest Editor

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Keywords

  • RNA structure
  • ribozymes
  • RNA-binding proteins
  • cotranscriptional and posttranscriptional processing
  • alternative splicing
  • splice factors and splice factor kinases
  • mRNA localisation, translation and decay
  • short and long noncoding RNAs

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Published Papers (2 papers)

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Research

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21 pages, 5698 KiB  
Article
Bioinformatics Screening of Potential Biomarkers from mRNA Expression Profiles to Discover Drug Targets and Agents for Cervical Cancer
by Md. Selim Reza, Md. Harun-Or-Roshid, Md. Ariful Islam, Md. Alim Hossen, Md. Tofazzal Hossain, Shengzhong Feng, Wenhui Xi, Md. Nurul Haque Mollah and Yanjie Wei
Int. J. Mol. Sci. 2022, 23(7), 3968; https://doi.org/10.3390/ijms23073968 - 2 Apr 2022
Cited by 23 | Viewed by 7310
Abstract
Bioinformatics analysis has been playing a vital role in identifying potential genomic biomarkers more accurately from an enormous number of candidates by reducing time and cost compared to the wet-lab-based experimental procedures for disease diagnosis, prognosis, and therapies. Cervical cancer (CC) is one [...] Read more.
Bioinformatics analysis has been playing a vital role in identifying potential genomic biomarkers more accurately from an enormous number of candidates by reducing time and cost compared to the wet-lab-based experimental procedures for disease diagnosis, prognosis, and therapies. Cervical cancer (CC) is one of the most malignant diseases seen in women worldwide. This study aimed at identifying potential key genes (KGs), highlighting their functions, signaling pathways, and candidate drugs for CC diagnosis and targeting therapies. Four publicly available microarray datasets of CC were analyzed for identifying differentially expressed genes (DEGs) by the LIMMA approach through GEO2R online tool. We identified 116 common DEGs (cDEGs) that were utilized to identify seven KGs (AURKA, BRCA1, CCNB1, CDK1, MCM2, NCAPG2, and TOP2A) by the protein–protein interaction (PPI) network analysis. The GO functional and KEGG pathway enrichment analyses of KGs revealed some important functions and signaling pathways that were significantly associated with CC infections. The interaction network analysis identified four TFs proteins and two miRNAs as the key transcriptional and post-transcriptional regulators of KGs. Considering seven KGs-based proteins, four key TFs proteins, and already published top-ranked seven KGs-based proteins (where five KGs were common with our proposed seven KGs) as drug target receptors, we performed their docking analysis with the 80 meta-drug agents that were already published by different reputed journals as CC drugs. We found Paclitaxel, Vinorelbine, Vincristine, Docetaxel, Everolimus, Temsirolimus, and Cabazitaxel as the top-ranked seven candidate drugs. Finally, we investigated the binding stability of the top-ranked three drugs (Paclitaxel, Vincristine, Vinorelbine) by using 100 ns MD-based MM-PBSA simulations with the three top-ranked proposed receptors (AURKA, CDK1, TOP2A) and observed their stable performance. Therefore, the proposed drugs might play a vital role in the treatment against CC. Full article
(This article belongs to the Special Issue Targeting Cancer through RNA Biology 2.0)
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Review

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17 pages, 2447 KiB  
Review
Mechanisms of Long Non-Coding RNAs in Biological Characteristics and Aerobic Glycolysis of Glioma
by Ningning Zhao, Jiajie Zhang, Qian Zhao, Chao Chen and Huijuan Wang
Int. J. Mol. Sci. 2021, 22(20), 11197; https://doi.org/10.3390/ijms222011197 - 18 Oct 2021
Cited by 16 | Viewed by 3923
Abstract
Glioma is the most common and aggressive tumor of the central nervous system. The uncontrolled proliferation, cellular heterogeneity, and diffusive capacity of glioma cells contribute to a very poor prognosis of patients with high grade glioma. Compared to normal cells, cancer cells exhibit [...] Read more.
Glioma is the most common and aggressive tumor of the central nervous system. The uncontrolled proliferation, cellular heterogeneity, and diffusive capacity of glioma cells contribute to a very poor prognosis of patients with high grade glioma. Compared to normal cells, cancer cells exhibit a higher rate of glucose uptake, which is accompanied with the metabolic switch from oxidative phosphorylation to aerobic glycolysis. The metabolic reprogramming of cancer cell supports excessive cell proliferation, which are frequently mediated by the activation of oncogenes or the perturbations of tumor suppressor genes. Recently, a growing body of evidence has started to reveal that long noncoding RNAs (lncRNAs) are implicated in a wide spectrum of biological processes in glioma, including malignant phenotypes and aerobic glycolysis. However, the mechanisms of diverse lncRNAs in the initiation and progression of gliomas remain to be fully unveiled. In this review, we summarized the diverse roles of lncRNAs in shaping the biological features and aerobic glycolysis of glioma. The thorough understanding of lncRNAs in glioma biology provides opportunities for developing diagnostic biomarkers and novel therapeutic strategies targeting gliomas. Full article
(This article belongs to the Special Issue Targeting Cancer through RNA Biology 2.0)
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