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Epitranscriptomics and Non-coding RNAs in Cancer
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Epitranscriptomics and Non-coding RNAs in Cancer

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (15 August 2022) | Viewed by 12795

Special Issue Editors

Dr. Mario Acunzo

E-Mail Website
Guest Editor
Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA
Interests: ncRNAs; epitranscriptomics; lung cancer; circulating biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanni Nigita

E-Mail Website
Guest Editor
Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA
Interests: computational biology; ncRNAs; epitranscriptomics; noncoding RNA editing; cancer informatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last several decades, breakthroughs in genetic sequencing and biotechnologies have led to identifying genes involved in the shifting cellular biology that characterizes hallmark cancer processes. Therefore, the activities of these genes must be tightly regulated to circumvent disease. One mechanism by which the cells exert control over gene activity is through finely tuned post-transcriptional modifications. Overall, there are greater than 150 such RNA modifications, including nucleotide substitutions (e.g., A-to-I, C-to-U), methylation (e.g., m6A, m1A, m5C, hm5C, 2'OMe), and pseudourylation (Ψ). The scope of "epitranscriptomics" research is to examine the consequences of such RNA modifications in human biology and disease. With the budding of exciting biotechnologies, such as high-throughput sequencing, researchers can better pinpoint epitranscriptomics modifications, thereby contributing to the expansion of this field. In particular, epitranscriptomics research has rapidly grown in the area that examines writers, readers, and erasers of various RNA modifications.

Post-transcriptional modifications affect both the coding and non-coding genome, with the majority of the genome being categorized as the latter. These non-coding regions were once thought to encode for "transcriptional noise," but perspectives have shifted over the last few decades. It is now understood that these non-coding genes have critical functions in regulating gene expression and cellular activity. Consequently, it is not surprising that perturbations within the non-coding genome have contributed to the pathology of many human diseases, including cancer. Therefore, the expression and activity of these non-coding genes must be tightly regulated.

This Special Issue in Genes will encompass both review and original research articles by experts in the field of epitranscriptomics and non-coding genetics, with a primary focus on cancer pathogenesis. These articles should highlight the progression and inherent challenges of these innovative fields. Moreover, this Special Issue aims to include epitranscriptome bioinformatics, including but not limited to novel software and computational approaches for the study of non-coding genetics and epitranscriptomics in cancer.

Dr. Mario Acunzo
Dr. Giovanni Nigita
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. Genes 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 2600 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

  • RNA editing
  • RNA methylation
  • Epitranscriptomics
  • Cancer
  • RNA modifications
  • Non-coding RNAs

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Published Papers (4 papers)

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Research

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11 pages, 1525 KiB  
Communication
Extracellular Vesicle MicroRNA in Malignant Pleural Effusion
by Samira Shojaee, Giulia Romano, Trinidad M. Sanchez, Gulmira Yermakhanova, Michela Saviana, Patricia Le, Giovanni Nigita, Federica Calore, Rachel Guthrie, Kathryn Hess, Le Kang, Theresa Swift-Scanlan, Jacob T. Graham, Najib M. Rahman, Patrick S. Nana-Sinkam and Mario Acunzo
Genes 2022, 13(11), 2159; https://doi.org/10.3390/genes13112159 - 19 Nov 2022
Cited by 6 | Viewed by 2473
Abstract
Lung and breast cancer are the two most common causes of malignant pleural effusion (MPE). MPE diagnosis plays a crucial role in determining staging and therapeutic interventions in these cancers. However, our understanding of the pathogenesis and progression of MPE at the molecular [...] Read more.
Lung and breast cancer are the two most common causes of malignant pleural effusion (MPE). MPE diagnosis plays a crucial role in determining staging and therapeutic interventions in these cancers. However, our understanding of the pathogenesis and progression of MPE at the molecular level is limited. Extracellular Vesicles (EVs) and their contents, including microRNAs (miRNAs), can be isolated from all bodily fluids, including pleural fluid. This study aims to compare EV-miRNA patterns of expression in MPE caused by breast (BA-MPE) and lung (LA-MPE) adenocarcinomas compared to the control group of heart-failure-induced effusions (HF-PE). We conducted an analysis of 24 pleural fluid samples (8 LA-MPE, 8 BA-MPE, and 8 HF-PE). Using NanoString technology, we profiled miRNAs within EVs isolated from 12 cases. Bioinformatic analysis demonstrated differential expression of miR-1246 in the MPE group vs. HF-PE group and miR-150-5p and miR-1246 in the BA-MPE vs. LA-MPE group, respectively. This difference was demonstrated and validated in an independent cohort using real-time PCR (RT-PCR). miRNA-1246 demonstrated 4-fold increased expression (OR: 3.87, 95% CI: 0.43, 35) in the MPE vs. HF-PE group, resulting in an area under the curve of 0.80 (95% CI: 0.60, 0.99). The highest accuracy for differentiating MPE vs. HF-PE was seen with a combination of miRNAs compared to each miRNA alone. Consistent with prior studies, this study demonstrates dysregulation of specific EV-based miRNAs in breast and lung cancer; pleural fluid provides direct access for the analysis of these EV-miRNAs as biomarkers and potential targets and may provide insight into the underlying pathogenesis of tumor progression. These findings should be explored in large prospective studies. Full article
(This article belongs to the Special Issue Epitranscriptomics and Non-coding RNAs in Cancer)
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12 pages, 2754 KiB  
Article
Abnormal Long Non-Coding RNAs Expression Patterns Have the Potential Ability for Predicting Survival and Treatment Response in Breast Cancer
by Ana Carolina Pavanelli, Flavia Rotea Mangone, Luciana R. C. Barros, Juliana Machado-Rugolo, Vera L. Capelozzi and Maria A. Nagai
Genes 2021, 12(7), 996; https://doi.org/10.3390/genes12070996 - 29 Jun 2021
Cited by 5 | Viewed by 2457
Abstract
Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival [...] Read more.
Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment. Full article
(This article belongs to the Special Issue Epitranscriptomics and Non-coding RNAs in Cancer)
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11 pages, 1515 KiB  
Article
CircVAMP3: A circRNA with a Role in Alveolar Rhabdomyosarcoma Cell Cycle Progression
by Francesca Rossi, Alvaro Centrón-Broco, Dario Dattilo, Gaia Di Timoteo, Marco Guarnacci, Alessio Colantoni, Manuel Beltran Nebot and Irene Bozzoni
Genes 2021, 12(7), 985; https://doi.org/10.3390/genes12070985 - 28 Jun 2021
Cited by 10 | Viewed by 2711
Abstract
Circular RNAs (circRNAs), a class of covalently closed RNAs formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in RH4, a representative cell line of alveolar [...] Read more.
Circular RNAs (circRNAs), a class of covalently closed RNAs formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in RH4, a representative cell line of alveolar rhabdomyosarcoma. We demonstrated that circVAMP3 has a differential m6A pattern opposed to its linear counterpart, suggesting that the two isoforms can be differently regulated by such RNA modification. Moreover, we show how circVAMP3 depletion in alveolar rhabdomyosarcoma cells can impair cell cycle progression, through the alteration of the AKT-related pathways, pointing to this non-coding RNA as a novel regulator of the alveolar rhabdomyosarcoma progression and as a putative future therapeutic target. Full article
(This article belongs to the Special Issue Epitranscriptomics and Non-coding RNAs in Cancer)
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Review

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27 pages, 1257 KiB  
Review
The Epitranscriptome in miRNAs: Crosstalk, Detection, and Function in Cancer
by Daniel del Valle-Morales, Patricia Le, Michela Saviana, Giulia Romano, Giovanni Nigita, Patrick Nana-Sinkam and Mario Acunzo
Genes 2022, 13(7), 1289; https://doi.org/10.3390/genes13071289 - 21 Jul 2022
Cited by 9 | Viewed by 4076
Abstract
The epitranscriptome encompasses all post-transcriptional modifications that occur on RNAs. These modifications can alter the function and regulation of their RNA targets, which, if dysregulated, result in various diseases and cancers. As with other RNAs, miRNAs are highly modified by epitranscriptomic modifications such [...] Read more.
The epitranscriptome encompasses all post-transcriptional modifications that occur on RNAs. These modifications can alter the function and regulation of their RNA targets, which, if dysregulated, result in various diseases and cancers. As with other RNAs, miRNAs are highly modified by epitranscriptomic modifications such as m6A methylation, 2′-O-methylation, m5C methylation, m7G methylation, polyuridine, and A-to-I editing. miRNAs are a class of small non-coding RNAs that regulates gene expression at the post-transcriptional level. miRNAs have gathered high clinical interest due to their role in disease, development, and cancer progression. Epitranscriptomic modifications alter the targeting, regulation, and biogenesis of miRNAs, increasing the complexity of miRNA regulation. In addition, emerging studies have revealed crosstalk between these modifications. In this review, we will summarize the epitranscriptomic modifications—focusing on those relevant to miRNAs—examine the recent crosstalk between these modifications, and give a perspective on how this crosstalk expands the complexity of miRNA biology. Full article
(This article belongs to the Special Issue Epitranscriptomics and Non-coding RNAs in Cancer)
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