绘制结直肠癌中的选择性剪接事件图谱。
Mapping alternative splicing events in colorectal cancer.
发表日期:2024 Jul 15
作者:
Yifeng Zheng, Guoqiang Zhong, Qiuyu Song, Haonan Zhang, Shanping Wang, Chuangzhen Lin, Chengcheng He, Mingsong Li
来源:
GENES & DEVELOPMENT
摘要:
尽管基因的异常剪接事件与结直肠癌(CRC)的发生和进展密切相关,但异常剪接事件的定位,特别是选择性剪接(AS)事件类型及其潜在影响仍处于研究阶段。在本研究中,我们分析了公共 RNA-seq 数据库 (GSE138202),并与健康个体相比,在 CRC 患者中确定了 14,314 个显着的 AS 事件。大多数参与CRC发生的关键基因(例如癌基因)具有不同的AS事件类型。此外,结果表明某些 AS 事件可能在参与剪接因子和 microRNA 的关键基因的功能中发挥重要作用。此外,我们观察到CRC中的癌基因CDK4倾向于发生外显子2跳跃AS事件,导致蛋白表达更倾向于与CCND1形成复合物,从而抑制细胞周期并削弱细胞增殖,同时增强细胞迁移能力。这些发现不仅为AS调节CRC的机制提供了新的见解,而且为CRC的靶向剪接治疗提供了理论基础。© 2024。作者。
Although aberrant splicing events of genes are closely related to the development and progression of colorectal cancer (CRC), the mapping of abnormal splicing events, especially alternative splicing (AS) event types and the underlying effects, remain investigational. In the present study, we analyzed a public RNA-seq database (GSE138202) and identified 14,314 significant AS events in CRC patients compared to healthy individuals. Most of the key genes such as oncogenes involved in the development of CRC have different AS event types. Moreover, the results demonstrate that certain AS events may play a significant role in the functioning of key genes involved in splicing factors and microRNAs. Furthermore, we observed that the oncogene CDK4 in CRC tends to undergo exon 2 skipping AS events, resulting in a stronger tendency for protein expression to form complexes with CCND1, thereby inhibiting the cell cycle and weakening cell proliferation, while enhancing cell migration capability. These findings not only provide new insights into the mechanism of AS in regulating CRC, but also offers a theoretical basis for targeted splicing therapy in CRC.© 2024. The Author(s).