MicroRNA and alternative mRNA splicing events in cancer drug response/resistance : potent therapeutic targets

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dc.contributor.author Marima, Rahaba
dc.contributor.author Francies, Flavia Zita
dc.contributor.author Hull, Rodney
dc.contributor.author Molefi, Thulo
dc.contributor.author Oyomno, Meryl
dc.contributor.author Khanyile, Richard
dc.contributor.author Mbatha, Sikhumbuzo Z.
dc.contributor.author Bates, David Owen
dc.contributor.author Dlamini, Zodwa
dc.date.accessioned 2022-07-15T06:23:24Z
dc.date.available 2022-07-15T06:23:24Z
dc.date.issued 2021-12-02
dc.description.abstract Cancer is a multifaceted disease that involves several molecular mechanisms including changes in gene expression. Two important processes altered in cancer that lead to changes in gene expression include altered microRNA (miRNA) expression and aberrant splicing events. MiRNAs are short non-coding RNAs that play a central role in regulating RNA silencing and gene expression. Alternative splicing increases the diversity of the proteome by producing several different spliced mRNAs from a single gene for translation. MiRNA expression and alternative splicing events are rigorously regulated processes. Dysregulation of miRNA and splicing events promote carcinogenesis and drug resistance in cancers including breast, cervical, prostate, colorectal, ovarian and leukemia. Alternative splicing may change the target mRNA 30UTR binding site. This alteration can affect the produced protein and may ultimately affect the drug affinity of target proteins, eventually leading to drug resistance. Drug resistance can be caused by intrinsic and extrinsic factors. The interplay between miRNA and alternative splicing is largely due to splicing resulting in altered 30UTR targeted binding of miRNAs. This can result in the altered targeting of these isoforms and altered drug targets and drug resistance. Furthermore, the increasing prevalence of cancer drug resistance poses a substantial challenge in the management of the disease. Henceforth, molecular alterations have become highly attractive drug targets to reverse the aberrant effects of miRNAs and splicing events that promote malignancy and drug resistance. While the miRNA–mRNA splicing interplay in cancer drug resistance remains largely to be elucidated, this review focuses on miRNA and alternative mRNA splicing (AS) events in breast, cervical, prostate, colorectal and ovarian cancer, as well as leukemia, and the role these events play in drug resistance. MiRNA induced cancer drug resistance; alternative mRNA splicing (AS) in cancer drug resistance; the interplay between AS and miRNA in chemoresistance will be discussed. Despite this great potential, the interplay between aberrant splicing events and miRNA is understudied but holds great potential in deciphering miRNA-mediated drug resistance. en_US
dc.description.department Maxillo-Facial and Oral Surgery en_US
dc.description.department Medical Oncology en_US
dc.description.department Surgery en_US
dc.description.librarian am2022 en_US
dc.description.sponsorship This research was funded by the South African Medical Research Council (SAMRC). en_US
dc.description.sponsorship The South African Medical Research Council (SAMRC) en_US
dc.description.uri https://www.mdpi.com/journal/biomedicines en_US
dc.identifier.citation Marima, R.; Francies, F.Z.; Hull, R.; Molefi, T.; Oyomno, M.; Khanyile, R.; Mbatha, S.; Mabongo, M.; Owen Bates, D.; Dlamini, Z. MicroRNA and Alternative mRNA Splicing Events in Cancer Drug Response/Resistance: Potent Therapeutic Targets. Biomedicines 2021, 9, 1818. https://DOI.org/10.3390/biomedicines9121818. en_US
dc.identifier.issn 2227-9059
dc.identifier.other 10.3390/biomedicines9121818
dc.identifier.uri https://repository.up.ac.za/handle/2263/86212
dc.language.iso en en_US
dc.publisher MDPI en_US
dc.rights © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. en_US
dc.subject MicroRNA (miRNA) en_US
dc.subject Alternative mRNA splicing (AS) en_US
dc.subject Drug resistance en_US
dc.subject Chemotherapy en_US
dc.title MicroRNA and alternative mRNA splicing events in cancer drug response/resistance : potent therapeutic targets en_US
dc.type Article en_US


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