Ebrahimie E, Rahimirad S, Tahsili M, Mohammadi-Dehcheshmeh M. Alternative RNA splicing in stem cells and cancer stem cells: Importance of transcript-based expression analysis. World J Stem Cells 2021; 13(10): 1394-1416 [PMID: 34786151 DOI: 10.4252/wjsc.v13.i10.1394]
Corresponding Author of This Article
Esmaeil Ebrahimie, PhD, Associate Professor, School of Animal and Veterinary Sciences, The University of Adelaide, No. 1 Mudla Wirra Rd, Roseworthy Campus, Adelaide 5005, South Australia, Australia. esmaeil.ebrahimie@adelaide.edu.au
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Esmaeil Ebrahimie, Manijeh Mohammadi-Dehcheshmeh, School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide 5005, South Australia, Australia
Esmaeil Ebrahimie, La Trobe Genomics Research Platform, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Melbourne 3086, Australia
Esmaeil Ebrahimie, School of Biosciences, The University of Melbourne, Melbourne 3010, Australia
Samira Rahimirad, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran 1497716316, Iran
Samira Rahimirad, Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal H4A 3J1, Quebec, Canada
Mohammadreza Tahsili, Department of Biology, University of Qom, Qom 3716146611, Iran
Author contributions: Ebrahimie E and Rahimirad S contributed equally in this study; Ebrahimie E conceived the idea of this manuscript; Rahimirad S, Tahsili M performed the literature review and initial data collection; Ebrahimie E, Rahimirad S wrote the manuscript; Mohammadi-Dehcheshmeh M performed figure preparation; Ebrahimie E, Mohammadi-Dehcheshmeh M edited and prepared the manuscript for submission; all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Esmaeil Ebrahimie, PhD, Associate Professor, School of Animal and Veterinary Sciences, The University of Adelaide, No. 1 Mudla Wirra Rd, Roseworthy Campus, Adelaide 5005, South Australia, Australia. esmaeil.ebrahimie@adelaide.edu.au
Received: March 18, 2021 Peer-review started: March 18, 2021 First decision: June 16, 2021 Revised: June 21, 2021 Accepted: September 14, 2021 Article in press: September 14, 2021 Published online: October 26, 2021 Processing time: 221 Days and 18 Hours
Abstract
Alternative ribonucleic acid (RNA) splicing can lead to the assembly of different protein isoforms with distinctive functions. The outcome of alternative splicing (AS) can result in a complete loss of function or the acquisition of new functions. There is a gap in knowledge of abnormal RNA splice variants promoting cancer stem cells (CSCs), and their prospective contribution in cancer progression. AS directly regulates the self-renewal features of stem cells (SCs) and stem-like cancer cells. Notably, octamer-binding transcription factor 4A spliced variant of octamer-binding transcription factor 4 contributes to maintaining stemness properties in both SCs and CSCs. The epithelial to mesenchymal transition pathway regulates the AS events in CSCs to maintain stemness. The alternative spliced variants of CSCs markers, including cluster of differentiation 44, aldehyde dehydrogenase, and doublecortin-like kinase, α6β1 integrin, have pivotal roles in increasing self-renewal properties and maintaining the pluripotency of CSCs. Various splicing analysis tools are considered in this study. LeafCutter software can be considered as the best tool for differential splicing analysis and identification of the type of splicing events. Additionally, LeafCutter can be used for efficient mapping splicing quantitative trait loci. Altogether, the accumulating evidence re-enforces the fact that gene and protein expression need to be investigated in parallel with alternative splice variants.
Core Tip: The alternative splicing machinery can produce various variants, associated with stemness characteristics of both stem cells (SCs) and cancer SCs. In this study, the role of spliced variants in SCs and stem-like cancer cells is reviewed. We highlight the importance of transcript-based expression concurrent with the gene and protein expression that leads to better understanding of self-renewal features of tumor cells.
