Manabile Mosebo Armstrong, Hull Rodney, Khanyile Richard, Molefi Thulo, Damane Botle Precious, Mongan Nigel Patrick, Bates David Owen, Dlamini Zodwa
SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0028, South Africa.
Department of Medical Oncology, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Pretoria 0028, South Africa.
Cancers (Basel). 2023 Aug 7;15(15):3999. doi: 10.3390/cancers15153999.
Colorectal 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.
结直肠癌（CRC）是全球癌症死亡的主要原因之一，其发病率呈上升趋势，尤其是在中低收入国家（LMICs）。有几个因素促成了结直肠癌的发生和发展。可变剪接（AS）被发现是结直肠癌发生和发展的分子机制之一。随着基因组/转录组测序和大型患者数据库的出现，异常可变剪接在癌症发生和发展中的广泛作用已变得清晰。可变剪接影响癌症的起始、增殖、侵袭和迁移。这些剪接变化通过产生数量改变的具有不同甚至相反功能的正常功能或新蛋白质来激活癌基因或使肿瘤抑制基因失活。因此，识别和表征结直肠癌特异性可变剪接事件和变体可能有助于设计新的治疗性剪接干扰药物。结直肠癌特异性剪接事件可用作诊断和预后生物标志物。在本综述中，将讨论可变剪接事件及其在结直肠癌发展中的作用。本文还综述了关于可变剪接事件的最新研究，这些事件可能被用作预后、诊断和靶向治疗指标。特别令人感兴趣的是靶向蛋白质精氨酸甲基转移酶（PMRT）异构体以开发新的治疗方法和诊断工具。还将讨论将这些发现转化为临床实践中的潜在挑战和局限性。
