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.
结直肠癌是全球癌症死亡率的主要原因之一，其发病率正在上升，尤其是在中低收入国家。多种因素共同促进结直肠癌的发生与发展。研究发现，可变剪接是结直肠癌发生发展的分子机制之一。随着基因组/转录组测序技术及大型患者数据库的发展，异常可变剪接在癌症发生发展中的广泛作用已日益明确。可变剪接影响癌症的起始、增殖、侵袭和迁移过程。这些剪接变化通过改变正常功能蛋白的产量或产生具有不同甚至相反功能的新蛋白，从而激活癌基因或使抑癌基因失活。因此，识别并表征结直肠癌特异性可变剪接事件及变异体，可能有助于设计新型治疗性剪接干扰药物。结直肠癌特异性剪接事件可作为诊断和预后的生物标志物。本文综述将讨论可变剪接事件及其在结直肠癌发展中的作用，同时回顾近期关于可变剪接事件作为预后、诊断及靶向治疗指标的研究进展。特别值得关注的是，靶向蛋白质精氨酸甲基转移酶亚型有望为开发新型治疗方法和诊断工具提供方向。文章也将探讨这些发现转化为临床实践过程中可能面临的挑战与局限性。
肿瘤(癌症)患者之家