Manabile, Mosebo ArmstrongHull, RodneyKhanyile, RichardMolefi, ThuloDamane, Botle PreciousMongan, Nigel PatrickBates, David OwenDlamini, Zodwa2024-04-182024-04-182023-08-07Manabile, M.A.; Hull, R.; Khanyile, R.; Molefi, T.; Damane, B.P.; Mongan, N.P.; Bates, D.O.; Dlamini, Z. Alternative Splicing Events and Their Clinical Significance in Colorectal Cancer: Targeted Therapeutic Opportunities. Cancers 2023, 15, 3999. https://DOI.org/10.3390/cancers15153999.2072-6694 (online)10.3390/cancers15153999http://hdl.handle.net/2263/95659Colorectal cancer (CRC) ranks as one of the top causes of cancer mortality worldwide and its incidence is on the rise, particularly in low-middle-income countries (LMICs). There are several factors that contribute to the development and progression of CRC. Alternative splicing (AS) was found to be one of the molecular mechanisms underlying the development and progression of CRC. With the advent of genome/transcriptome sequencing and large patient databases, the broad role of aberrant AS in cancer development and progression has become clear. AS affects cancer initiation, proliferation, invasion, and migration. These splicing changes activate oncogenes or deactivate tumor suppressor genes by producing altered amounts of normally functional or new proteins with different, even opposing, functions. Thus, identifying and characterizing CRC-specific alternative splicing events and variants might help in designing new therapeutic splicing disrupter drugs. CRC-specific splicing events can be used as diagnostic and prognostic biomarkers. In this review, alternatively spliced events and their role in CRC development will be discussed. The paper also reviews recent research on alternatively spliced events that might be exploited as prognostic, diagnostic, and targeted therapeutic indicators. Of particular interest is the targeting of protein arginine methyltransferase (PMRT) isoforms for the development of new treatments and diagnostic tools. The potential challenges and limitations in translating these discoveries into clinical practice will also be addressed.en© 2023 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.Alternative splicingProtein arginine methyltransferasesSplicing factor kinasesAS eventsSplicing disrupter drugsPRMT isoformsPRMT inhibitorsColorectal cancer (CRC)Low- and middle-income countries (LMICs)Protein arginine methyltransferase (PMRT)SDG-03: Good health and well-beingArticle