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The Emerging Role of RNA in Diseases and Cancers 2.0
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The Emerging Role of RNA in Diseases and Cancers 2.0

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 4243

Special Issue Editor

Prof. Dr. Alessandro Fatica

E-Mail Website
Guest Editor
Department of Biology and Biotechnology ‘Charles Darwin’, Sapienza University of Rome, 00185 Rome, Italy
Interests: RNA modifications; gene expression regulation; leukemia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our 2022 Special Issue “The Emerging Role of RNA in Diseases and Cancers”.

Cellular functions are controlled by the correct expression of both protein-coding RNAs and non-coding RNAs. The proper expression, maturation and function of these different classes of RNA depend on specific interactions with RNA-binding proteins, the chemical modification of nucleotides and also sequence editing. The dysregulation of any of these processes can cause aberrant gene expression and, eventually, contribute to diseases and carcinogenesis.

This Special Issue aims to discuss the role of RNA in diseases and cancer. In particular, topics such as the function of regulatory non-coding RNAs (microRNAs, lncRNAs and circRNAs), the impact of the chemical modification of RNA (rRNAs, tRNAs and mRNAs), RNA editing, and the role of RNA-binding proteins will be addressed in this Special Issue. This Special Issue aims to provide an in-depth picture at the molecular level of the mechanisms of action that regulate RNA function in diseases and cancers.

Prof. Dr. Alessandro Fatica
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • long non-coding RNAs
  • microRNAs
  • circular RNAs
  • RNA modifications
  • RNA editing
  • mRNA translation
  • alternative splicing
  • RNA and protein aggregation
  • RNA-binding proteins

Published Papers (4 papers)

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Research

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30 pages, 3850 KiB  
Article
Effects of In Utero EtOH Exposure on 18S Ribosomal RNA Processing: Contribution to Fetal Alcohol Spectrum Disorder
by Nune Darbinian, Gary L. Gallia, Armine Darbinyan, Ekaterina Vadachkoria, Nana Merabova, Amos Moore, Laura Goetzl, Shohreh Amini and Michael E. Selzer
Int. J. Mol. Sci. 2023, 24(18), 13714; https://doi.org/10.3390/ijms241813714 - 05 Sep 2023
Viewed by 1000
Abstract
Fetal alcohol spectrum disorders (FASD) are leading causes of neurodevelopmental disability. The mechanisms by which alcohol (EtOH) disrupts fetal brain development are incompletely understood, as are the genetic factors that modify individual vulnerability. Because the phenotype abnormalities of FASD are so varied and [...] Read more.
Fetal alcohol spectrum disorders (FASD) are leading causes of neurodevelopmental disability. The mechanisms by which alcohol (EtOH) disrupts fetal brain development are incompletely understood, as are the genetic factors that modify individual vulnerability. Because the phenotype abnormalities of FASD are so varied and widespread, we investigated whether fetal exposure to EtOH disrupts ribosome biogenesis and the processing of pre-ribosomal RNAs and ribosome assembly, by determining the effect of exposure to EtOH on the developmental expression of 18S rRNA and its cleaved forms, members of a novel class of short non-coding RNAs (srRNAs). In vitro neuronal cultures and fetal brains (11–22 weeks) were collected according to an IRB-approved protocol. Twenty EtOH-exposed brains from the first and second trimester were compared with ten unexposed controls matched for gestational age and fetal gender. Twenty fetal-brain-derived exosomes (FB-Es) were isolated from matching maternal blood. RNA was isolated using Qiagen RNA isolation kits. Fetal brain srRNA expression was quantified by ddPCR. srRNAs were expressed in the human brain and FB-Es during fetal development. EtOH exposure slightly decreased srRNA expression (1.1-fold; p = 0.03). Addition of srRNAs to in vitro neuronal cultures inhibited EtOH-induced caspase-3 activation (1.6-fold, p = 0.002) and increased cell survival (4.7%, p = 0.034). The addition of exogenous srRNAs reversed the EtOH-mediated downregulation of srRNAs (2-fold, p = 0.002). EtOH exposure suppressed expression of srRNAs in the developing brain, increased activity of caspase-3, and inhibited neuronal survival. Exogenous srRNAs reversed this effect, possibly by stabilizing endogenous srRNAs, or by increasing the association of cellular proteins with srRNAs, modifying gene transcription. Finally, the reduction in 18S rRNA levels correlated closely with the reduction in fetal eye diameter, an anatomical hallmark of FASD. The findings suggest a potential mechanism for EtOH-mediated neurotoxicity via alterations in 18S rRNA processing and the use of FB-Es for early diagnosis of FASD. Ribosome biogenesis may be a novel target to ameliorate FASD in utero or after birth. These findings are consistent with observations that gene–environment interactions contribute to FASD vulnerability. Full article
(This article belongs to the Special Issue The Emerging Role of RNA in Diseases and Cancers 2.0)
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17 pages, 4806 KiB  
Article
Transcriptional Response to Standard AML Drugs Identifies Synergistic Combinations
by Piyush More, Joëlle Aurelie Mekontso Ngaffo, Ute Goedtel-Armbrust, Patricia S. Hähnel, Udo F. Hartwig, Thomas Kindler and Leszek Wojnowski
Int. J. Mol. Sci. 2023, 24(16), 12926; https://doi.org/10.3390/ijms241612926 - 18 Aug 2023
Viewed by 999
Abstract
Unlike genomic alterations, gene expression profiles have not been widely used to refine cancer therapies. We analyzed transcriptional changes in acute myeloid leukemia (AML) cell lines in response to standard first-line AML drugs cytarabine and daunorubicin by means of RNA sequencing. Those changes [...] Read more.
Unlike genomic alterations, gene expression profiles have not been widely used to refine cancer therapies. We analyzed transcriptional changes in acute myeloid leukemia (AML) cell lines in response to standard first-line AML drugs cytarabine and daunorubicin by means of RNA sequencing. Those changes were highly cell- and treatment-specific. By comparing the changes unique to treatment-sensitive and treatment-resistant AML cells, we enriched for treatment-relevant genes. Those genes were associated with drug response-specific pathways, including calcium ion-dependent exocytosis and chromatin remodeling. Pharmacological mimicking of those changes using EGFR and MEK inhibitors enhanced the response to daunorubicin with minimum standalone cytotoxicity. The synergistic response was observed even in the cell lines beyond those used for the discovery, including a primary AML sample. Additionally, publicly available cytotoxicity data confirmed the synergistic effect of EGFR inhibitors in combination with daunorubicin in all 60 investigated cancer cell lines. In conclusion, we demonstrate the utility of treatment-evoked gene expression changes to formulate rational drug combinations. This approach could improve the standard AML therapy, especially in older patients. Full article
(This article belongs to the Special Issue The Emerging Role of RNA in Diseases and Cancers 2.0)
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15 pages, 1515 KiB  
Article
Comprehensive Analysis of Circular RNAs in Endothelial Cells
by Sabina Lichołai, Dorota Studzińska, Hanna Plutecka, Tomasz Gubała and Marek Sanak
Int. J. Mol. Sci. 2023, 24(12), 10025; https://doi.org/10.3390/ijms241210025 - 12 Jun 2023
Cited by 2 | Viewed by 896
Abstract
Non-coding RNAs constitute a heterogeneous group of molecules that lack the ability to encode proteins but retain the potential ability to influence cellular processes through a regulatory mechanism. Of these proteins, microRNAs, long non-coding RNAs, and more recently, circular RNAs have been the [...] Read more.
Non-coding RNAs constitute a heterogeneous group of molecules that lack the ability to encode proteins but retain the potential ability to influence cellular processes through a regulatory mechanism. Of these proteins, microRNAs, long non-coding RNAs, and more recently, circular RNAs have been the most extensively described. However, it is not entirely clear how these molecules interact with each other. For circular RNAs, the basics of their biogenesis and properties are also lacking. Therefore, in this study we performed a comprehensive analysis of circular RNAs in relation to endothelial cells. We identified the pool of circular RNAs present in the endothelium and showed their spectrum and expression across the genome. Using different computational strategies, we proposed approaches to search for potentially functional molecules. In addition, using data from an in vitro model that mimics conditions in the endothelium of an aortic aneurysm, we demonstrated altered expression levels of circRNAs mediated by microRNAs. Full article
(This article belongs to the Special Issue The Emerging Role of RNA in Diseases and Cancers 2.0)
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Review

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16 pages, 1007 KiB  
Review
The Role of miRNAs in Childhood Acute Lymphoblastic Leukemia Relapse and the Associated Molecular Mechanisms
by Dalia Barrios-Palacios, Jorge Organista-Nava, Juan Carlos Balandrán, Luz del Carmen Alarcón-Romero, Ma Isabel Zubillaga-Guerrero, Berenice Illades-Aguiar, Alinne Ayulieth Rivas-Alarcón, Jessica Julieth Diaz-Lucas, Yazmín Gómez-Gómez and Marco Antonio Leyva-Vázquez
Int. J. Mol. Sci. 2024, 25(1), 119; https://doi.org/10.3390/ijms25010119 (registering DOI) - 21 Dec 2023
Viewed by 807
Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer in children worldwide. Although ALL patients’ overall survival rates in wealthy countries currently surpass 80%, 15–20% of patients still experience relapse. The underlying mechanisms of relapse are still not fully understood, and little progress [...] Read more.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children worldwide. Although ALL patients’ overall survival rates in wealthy countries currently surpass 80%, 15–20% of patients still experience relapse. The underlying mechanisms of relapse are still not fully understood, and little progress has been made in treating refractory or relapsed disease. Disease relapse and treatment failure are common causes of leukemia-related death. In ALL relapse, several gene signatures have been identified, but it is also important to study miRNAs involved in ALL relapse in an effort to avoid relapse and to achieve better survival rates since miRNAs regulate target genes that participate in signaling pathways involved in relapse, such as those related to drug resistance, survival signals, and antiapoptotic mechanisms. Several miRNAs, such as miR-24, miR-27a, miR-99/100, miR-124, miR-1225b, miR-128b, miR-142-3p, miR-155 and miR-335-3p, are valuable biomarkers for prognosis and treatment response in ALL patients. Thus, this review aimed to analyze the primary miRNAs involved in pediatric ALL relapse and explore the underlying molecular mechanisms in an effort to identify miRNAs that may be potential candidates for anti-ALL therapy soon. Full article
(This article belongs to the Special Issue The Emerging Role of RNA in Diseases and Cancers 2.0)
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