Current Strategies to Investigate the Role of ncRNAs in Carcinogenesis

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 9742

Special Issue Editor


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Guest Editor
Center for Integrated Microbiome and Chronobiology Research, Rush University, 1653 W Congress Pkwy #12, Chicago, IL 60612, USA
Interests: bioinformatic data analysis; next-generation sequencing; RNA biology; biochemistry

Special Issue Information

Dear Colleagues,

Carcinogenesis is a multistep process in which normal cells acquire genetic and epigenetic alterations that drive the onset of “hallmarks” of cancer, finally resulting in the development and progression of malignancies. Recent discoveries of the role of non-coding RNAs (ncRNAs) in these malignancies are a promising frontier of cancer genomics. ncRNAs can affect cancer cell fate and survival through a variety of different mechanisms, including transcriptional and post-transcriptional modification, chromatin remodeling, and signal transduction. However, to date, the exact function and mechanism of action of most of them is still unknown. As far as we know, ncRNAs create a complex network of mutual interactions and act as oncogenes or tumor suppressors. The understanding of the role of ncRNAs in tumorigenesis is a challenging goal in current biology.

Recently, profiling and next-generation sequencing (NGS) of ncRNAs have disclosed deep deregulation in human cancers, mostly due to aberrant mechanisms of ncRNAs biogenesis, such as amplification, deletion, abnormal epigenetic or transcriptional regulation. Additionally, the development of new bioinformatic tools has provided a unique opportunity to study transcriptome-wide ncRNA functions in carcinogenesis.

The aim of this Special Issue is to compile currently available computational and experimental strategies to investigate ncRNAs in cancer. We hope that this compendium will provide critical insights into the relevance of ncRNAs in cancer biology.

Dr. Deepak Sharma
Guest Editor

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Keywords

  • carcinogenesis
  • next-generation sequencing (NGS)
  • bioinformatics
  • genomics
  • cancer biology
  • ncRNA in cancer

Published Papers (5 papers)

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Research

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9 pages, 1757 KiB  
Communication
Inverse Modulation of Aurora Kinase A and Topoisomerase IIα in Normal and Tumor Breast Cells upon Knockdown of Mitochondrial ASncmtRNA
by Maximiliano F. Bendek, Christopher Fitzpatrick, Emanuel Jeldes, Anne Boland, Jean-François Deleuze, Nicole Farfán, Jaime Villegas, Gino Nardocci, Martín Montecino, Luis O. Burzio and Verónica A. Burzio
Non-Coding RNA 2023, 9(5), 59; https://doi.org/10.3390/ncrna9050059 - 02 Oct 2023
Cited by 1 | Viewed by 2057
Abstract
Breast cancer is currently the most diagnosed form of cancer and the leading cause of death by cancer among females worldwide. We described the family of long non-coding mitochondrial RNAs (ncmtRNAs), comprised of sense (SncmtRNA) and antisense (ASncmtRNA) members. Knockdown of ASncmtRNAs using [...] Read more.
Breast cancer is currently the most diagnosed form of cancer and the leading cause of death by cancer among females worldwide. We described the family of long non-coding mitochondrial RNAs (ncmtRNAs), comprised of sense (SncmtRNA) and antisense (ASncmtRNA) members. Knockdown of ASncmtRNAs using antisense oligonucleotides (ASOs) induces proliferative arrest and apoptotic death of tumor cells, but not normal cells, from various tissue origins. In order to study the mechanisms underlying this selectivity, in this study we performed RNAseq in MDA-MB-231 breast cancer cells transfected with ASncmtRNA-specific ASO or control-ASO, or left untransfected. Bioinformatic analysis yielded several differentially expressed cell-cycle-related genes, from which we selected Aurora kinase A (AURKA) and topoisomerase IIα (TOP2A) for RT-qPCR and western blot validation in MDA-MB-231 and MCF7 breast cancer cells, as well as normal breast epithelial cells (HMEC). We observed no clear differences regarding mRNA levels but both proteins were downregulated in tumor cells and upregulated in normal cells. Since these proteins play a role in genomic integrity, this inverse effect of ASncmtRNA knockdown could account for tumor cell downfall whilst protecting normal cells, suggesting this approach could be used for genomic protection under cancer treatment regimens or other scenarios. Full article
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15 pages, 1969 KiB  
Article
Investigation into the Role of Long-Non-Coding RNA MIAT in Leukemia
by Alessia Ostini and Mirna Mourtada-Maarabouni
Non-Coding RNA 2023, 9(4), 47; https://doi.org/10.3390/ncrna9040047 - 11 Aug 2023
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Abstract
Myocardial Infarction Associated Transcript (MIAT) is a nuclear long non-coding RNA (LncRNA) with four different splicing variants. MIAT dysregulation is associated with carcinogenesis, mainly acting as an oncogene regulating cellular growth, invasion, and metastasis. The aim of the current study is [...] Read more.
Myocardial Infarction Associated Transcript (MIAT) is a nuclear long non-coding RNA (LncRNA) with four different splicing variants. MIAT dysregulation is associated with carcinogenesis, mainly acting as an oncogene regulating cellular growth, invasion, and metastasis. The aim of the current study is to investigate the role of MIAT in the regulation of T and chronic myeloid leukemic cell survival. To this end, MIAT was silenced using MIAT-specific siRNAs in leukemic cell lines, and functional assays were performed thereafter. This investigation also aims to investigate the effects of MIAT silencing on the expression of core genes involved in cancer. Functional studies and gene expression determination confirm that MIAT knockdown not only affects short- and long-term survival and the apoptosis of leukemic cells but also plays a pivotal role in the alteration of key genes involved in cancer, including c-MYC and HIF-1A. Our observations suggest that MIAT could act as an oncogene and it has the potential to be used not only as a reliable biomarker for leukemia, but also be employed for prognostic and therapeutic purposes. Full article
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Review

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27 pages, 1517 KiB  
Review
miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine
by Roberto Piergentili, Enrico Marinelli, Gaspare Cucinella, Alessandra Lopez, Gabriele Napoletano, Giuseppe Gullo and Simona Zaami
Non-Coding RNA 2024, 10(2), 16; https://doi.org/10.3390/ncrna10020016 - 21 Feb 2024
Viewed by 1370
Abstract
Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in [...] Read more.
Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to tumor development and angiogenesis in different types of cancer. Recently, complex interactions among coding and non-coding RNA have been elucidated, further shedding light on the complexity of the roles these molecules fulfill in cancer formation. In this context, knowledge about the role of miR in BC has significantly improved, highlighting the deregulation of these molecules as additional factors influencing BC occurrence, development and classification. A considerable number of papers has been published over the past few years regarding the role of miR-125 in human pathology in general and in several types of cancer formation in particular. Interestingly, miR-125 family members have been recently linked to BC formation as well, and complex interactions (competing endogenous RNA networks, or ceRNET) between this molecule and target mRNA have been described. In this review, we summarize the state-of-the-art about research on this topic. Full article
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30 pages, 37976 KiB  
Review
Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma
by Nor Hayati Ismail, Ali Mussa, Mutaz Jamal Al-Khreisat, Shafini Mohamed Yusoff, Azlan Husin, Hamid Ali Nagi Al-Jamal, Muhammad Farid Johan and Md Asiful Islam
Non-Coding RNA 2023, 9(6), 68; https://doi.org/10.3390/ncrna9060068 - 03 Nov 2023
Cited by 2 | Viewed by 1697
Abstract
The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs [...] Read more.
The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs can serve as oncogenes or tumor suppressors depending on the target genes. In MM, miRNA disruption could result in abnormal gene expression responsible for cell growth, apoptosis, and other biological processes pertinent to cancer development. The dysregulated miRNAs inhibit the activity of tumor suppressor genes, contributing to disease progression. Nonetheless, several miRNAs are downregulated in MM and have been identified as gene regulators implicated in extracellular matrix remodeling and cell adhesion. miRNA depletion potentially facilitates the tumor advancement and resistance of therapeutic drugs. Additionally, lncRNAs are key regulators of numerous cellular processes, such as gene expression, chromatin remodeling, protein trafficking, and recently linked MM development. The lncRNAs are uniquely expressed and influence gene expression that supports MM growth, in addition to facilitating cellular proliferation and viability via multiple molecular pathways. miRNA and lncRNA alterations potentially result in anomalous gene expression and interfere with the regular functioning of MM. Thus, this review aims to highlight the dysregulation of these ncRNAs, which engender novel therapeutic modalities for the treatment of MM. Full article
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Other

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32 pages, 2038 KiB  
Systematic Review
The Potential microRNA Prognostic Signature in HNSCCs: A Systematic Review
by Mario Dioguardi, Francesca Spirito, Giovanna Iacovelli, Diego Sovereto, Enrica Laneve, Luigi Laino, Giorgia Apollonia Caloro, Ari Qadir Nabi, Andrea Ballini, Lorenzo Lo Muzio and Giuseppe Troiano
Non-Coding RNA 2023, 9(5), 54; https://doi.org/10.3390/ncrna9050054 - 14 Sep 2023
Cited by 1 | Viewed by 1715
Abstract
Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive [...] Read more.
Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as “signature microRNA OR miR” AND “HNSCC OR LSCC OR OSCC OR oral cancer” were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination. Full article
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