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Biomolecules
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Non-coding RNAs in Cancer Biology
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Non-coding RNAs in Cancer Biology

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (25 February 2022) | Viewed by 16852

Special Issue Editor

Dr. Ryou-u Takahashi

E-Mail Website
Guest Editor
Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Interests: senescence; aging; microRNA; cancer stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances on next generation sequencing technologies reveal that, in addition to canonical protein-coding genes and well-known RNAs such as rRNA, tRNA and snoRNA, a large number of non-coding RNAs (ncRNAs) that lack protein-coding capacity are transcribed from human genome. Accumulating the lines of evidence indicate that ncRNAs such as microRNA (miRNA), long non-coding RNA (lncRNA) and tRNA-derived RNA fragment (tRF) play important roles in diverse biological phenomena such as stem cell maintenance, tissue development and aging. Therefore, aberrant expression of these ncRNAs is associated with disease onset and development including cancer. In cancer biology, multiple studies reported that dysregulation of ncRNA is associated with various steps of tumor malignancy such as tumor initiation, drug-resistance and metastasis.

This Special Issue of Biomolecules will cover the following important aspects of ncRNA functions in cancer biology:

  • biosynthesis of ncRNAs and their roles in gene regulation;
  • roles of ncRNAs in cancer biology such as tumor initiation, drug resistance and metastasis;
  • therapeutic potential of ncRNAs for cancer treatment;
  • novel methods and applications for the delivery of ncRNAs.

Dr. Ryou-u Takahashi
Guest Editor

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. Biomolecules 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 2700 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.

Published Papers (5 papers)

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Research

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12 pages, 6438 KiB  
Article
Gallic Acid Derivatives Propyl Gallate and Epigallocatechin Gallate Reduce rRNA Transcription via Induction of KDM2A Activation
by Yuji Tanaka and Makoto Tsuneoka
Biomolecules 2022, 12(1), 30; https://doi.org/10.3390/biom12010030 - 25 Dec 2021
Cited by 9 | Viewed by 2814
Abstract
We previously reported that lysine-demethylase 2A (KDM2A), a Jumonji-C histone demethylase, is activated by gallic acid to reduce H3K36me2 levels in the rRNA gene promoter and consequently inhibit rRNA transcription and cell proliferation in the breast cancer cell line MCF-7. Gallic acid activates [...] Read more.
We previously reported that lysine-demethylase 2A (KDM2A), a Jumonji-C histone demethylase, is activated by gallic acid to reduce H3K36me2 levels in the rRNA gene promoter and consequently inhibit rRNA transcription and cell proliferation in the breast cancer cell line MCF-7. Gallic acid activates AMP-activated protein kinase (AMPK) and increases reactive oxygen species (ROS) production to activate KDM2A. Esters of gallic acid, propyl gallate (PG) and epigallocatechin gallate (EGCG), and other chemicals, reduce cancer cell proliferation. However, whether these compounds activate KDM2A has yet to be tested. In this study, we found that PG and EGCG decreased rRNA transcription and cell proliferation through KDM2A in MCF-7 cells. The activation of both AMPK and ROS production by PG or EGCG was required to activate KDM2A. Of note, while the elevation of ROS production by PG or EGCG was limited in time, it was sufficient to activate KDM2A. Importantly, the inhibition of rRNA transcription and cell proliferation by gallic acid, PG, or EGCG was specifically observed in MCF-7 cells, whereas it was not observed in non-tumorigenic MCF10A cells. Altogether, these results suggest that the derivatization of gallic acid may be used to obtain new compounds with anti-cancer activity. Full article
(This article belongs to the Special Issue Non-coding RNAs in Cancer Biology)
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14 pages, 3597 KiB  
Article
Characterization of miR-34a-Induced Epithelial–Mesenchymal Transition in Non-Small Lung Cancer Cells Focusing on p53
by Masashi Kawami, Shinnosuke Takenaka, Mizuki Akai, Ryoko Yumoto and Mikihisa Takano
Biomolecules 2021, 11(12), 1853; https://doi.org/10.3390/biom11121853 - 9 Dec 2021
Cited by 5 | Viewed by 2382
Abstract
Background: Epithelial–mesenchymal transition (EMT), a phenotypic conversion of the epithelial to mesenchymal state, contributes to cancer progression. Currently, several microRNAs (miRNAs) are associated with EMT-mediated cancer progression, but the contribution of miR-34a to EMT in cancer cells remains controversial. The present study aimed [...] Read more.
Background: Epithelial–mesenchymal transition (EMT), a phenotypic conversion of the epithelial to mesenchymal state, contributes to cancer progression. Currently, several microRNAs (miRNAs) are associated with EMT-mediated cancer progression, but the contribution of miR-34a to EMT in cancer cells remains controversial. The present study aimed to clarify the role of miR-34a in the EMT-related phenotypes of human non-small cell lung cancer (NSCLC) cell lines, A549 (p53 wild-type) and H1299 (p53-deficient). Methods: The miR-34a mimic and p53 small interfering RNA (siRNA) were transfected into the cells using Lipofectamine, and the obtained total RNA and cell lysates were used for real-time polymerase chain reaction and Western blotting analysis, respectively. Results: The introduction of the miR-34a mimic led to an increase in the mRNA and protein expression levels of α-smooth muscle actin (α-SMA), a mesenchymal marker gene, in A549, but not in H1299 cells. Additionally, miR-34a-induced the upregulation of p53 activity and migration was observed in A549, but not in H1299 cells. However, under the p53-knockdown condition, only α-SMA upregulation by miR-34a was abolished. Conclusion: These findings indicate a close relationship between p53 and miR-34a-induced EMT in p53-wild type NSCLC cells, which provides novel insights about the role of miR-34a in EMT-like phenotypic changes in NSCLC. Full article
(This article belongs to the Special Issue Non-coding RNAs in Cancer Biology)
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Review

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11 pages, 667 KiB  
Review
Making Invisible RNA Visible: Discriminative Sequencing Methods for RNA Molecules with Specific Terminal Formations
by Megumi Shigematsu and Yohei Kirino
Biomolecules 2022, 12(5), 611; https://doi.org/10.3390/biom12050611 - 20 Apr 2022
Cited by 5 | Viewed by 2367
Abstract
Next generation sequencing of RNA molecules (RNA-seq) has become a common tool to characterize the expression profiles of RNAs and their regulations in normal physiological processes and diseases. Although increasingly accumulating RNA-seq data are widely available through publicly accessible sites, most of the [...] Read more.
Next generation sequencing of RNA molecules (RNA-seq) has become a common tool to characterize the expression profiles of RNAs and their regulations in normal physiological processes and diseases. Although increasingly accumulating RNA-seq data are widely available through publicly accessible sites, most of the data for short non-coding RNAs (sncRNAs) have been obtained for microRNA (miRNA) analyses by standard RNA-seq, which only capture the sncRNAs with 5′-phosphate (5′-P) and 3′-hydroxyl (3′-OH) ends. The sncRNAs with other terminal formations such as those with a 5′-hydroxyl end (5′-OH), a 3′-phosphate (3′-P) end, or a 2′,3′-cyclic phosphate end (2′,3′-cP) cannot be efficiently amplified and sequenced by standard RNA-seq. Due to the invisibility in standard RNA-seq data, these non-miRNA-sncRNAs have been a hidden component in the transcriptome. However, as the functional significances of these sncRNAs have become increasingly apparent, specific RNA-seq methods compatible with various terminal formations of sncRNAs have been developed and started shedding light on the previously unrecognized sncRNAs that lack 5′-P/3′-OH ends. In this review, we summarize the expanding world of sncRNAs with various terminal formations and the strategic approaches of specific RNA-seq methods to distinctively characterize their expression profiles. Full article
(This article belongs to the Special Issue Non-coding RNAs in Cancer Biology)
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47 pages, 2607 KiB  
Review
Epigenetic Regulation in Exposome-Induced Tumorigenesis: Emerging Roles of ncRNAs
by Miguel Ángel Olmedo-Suárez, Ivonne Ramírez-Díaz, Andrea Pérez-González, Alejandro Molina-Herrera, Miguel Ángel Coral-García, Sagrario Lobato, Pouya Sarvari, Guillermo Barreto and Karla Rubio
Biomolecules 2022, 12(4), 513; https://doi.org/10.3390/biom12040513 - 28 Mar 2022
Cited by 3 | Viewed by 5421
Abstract
Environmental factors, including pollutants and lifestyle, constitute a significant role in severe, chronic pathologies with an essential societal, economic burden. The measurement of all environmental exposures and assessing their correlation with effects on individual health is defined as the exposome, which interacts with [...] Read more.
Environmental factors, including pollutants and lifestyle, constitute a significant role in severe, chronic pathologies with an essential societal, economic burden. The measurement of all environmental exposures and assessing their correlation with effects on individual health is defined as the exposome, which interacts with our unique characteristics such as genetics, physiology, and epigenetics. Epigenetics investigates modifications in the expression of genes that do not depend on the underlying DNA sequence. Some studies have confirmed that environmental factors may promote disease in individuals or subsequent progeny through epigenetic alterations. Variations in the epigenetic machinery cause a spectrum of different disorders since these mechanisms are more sensitive to the environment than the genome, due to the inherent reversible nature of the epigenetic landscape. Several epigenetic mechanisms, including modifications in DNA (e.g., methylation), histones, and noncoding RNAs can change genome expression under the exogenous influence. Notably, the role of long noncoding RNAs in epigenetic processes has not been well explored in the context of exposome-induced tumorigenesis. In the present review, our scope is to provide relevant evidence indicating that epigenetic alterations mediate those detrimental effects caused by exposure to environmental toxicants, focusing mainly on a multi-step regulation by diverse noncoding RNAs subtypes. Full article
(This article belongs to the Special Issue Non-coding RNAs in Cancer Biology)
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22 pages, 2330 KiB  
Review
Impact of Non-Coding RNAs on Chemotherapeutic Resistance in Oral Cancer
by Karen Yamaguchi, Tomofumi Yamamoto, Junichiro Chikuda, Tatsuo Shirota and Yusuke Yamamoto
Biomolecules 2022, 12(2), 284; https://doi.org/10.3390/biom12020284 - 9 Feb 2022
Cited by 9 | Viewed by 3110
Abstract
Drug resistance in oral cancer is one of the major problems in oral cancer therapy because therapeutic failure directly results in tumor recurrence and eventually in metastasis. Accumulating evidence has demonstrated the involvement of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long [...] Read more.
Drug resistance in oral cancer is one of the major problems in oral cancer therapy because therapeutic failure directly results in tumor recurrence and eventually in metastasis. Accumulating evidence has demonstrated the involvement of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in processes related to the development of drug resistance. A number of studies have shown that ncRNAs modulate gene expression at the transcriptional or translational level and regulate biological processes, such as epithelial-to-mesenchymal transition, apoptosis, DNA repair and drug efflux, which are tightly associated with drug resistance acquisition in many types of cancer. Interestingly, these ncRNAs are commonly detected in extracellular vesicles (EVs) and are known to be delivered into surrounding cells. This intercellular communication via EVs is currently considered to be important for acquired drug resistance. Here, we review the recent advances in the study of drug resistance in oral cancer by mainly focusing on the function of ncRNAs, since an increasing number of studies have suggested that ncRNAs could be therapeutic targets as well as biomarkers for cancer diagnosis. Full article
(This article belongs to the Special Issue Non-coding RNAs in Cancer Biology)
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