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绘制结直肠癌中的可变剪接事件图谱。

Mapping alternative splicing events in colorectal cancer.

作者信息

Zheng Yifeng, Zhong Guoqiang, Song Qiuyu, Zhang Haonan, Wang Shanping, Lin Chuangzhen, He Chengcheng, Li Mingsong

机构信息

Department of Gastroenterology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

出版信息

Discov Oncol. 2024 Jul 15;15(1):280. doi: 10.1007/s12672-024-01149-z.

Abstract

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.

摘要

尽管基因的异常剪接事件与结直肠癌(CRC)的发生和发展密切相关,但异常剪接事件的图谱,尤其是可变剪接(AS)事件类型及其潜在影响仍在研究中。在本研究中,我们分析了一个公共RNA测序数据库(GSE138202),并确定了与健康个体相比,CRC患者中有14314个显著的AS事件。大多数参与CRC发生的关键基因,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微小RNA的关键基因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,导致蛋白质表达与CCND1形成复合物的趋势更强,从而抑制细胞周期并减弱细胞增殖,同时增强细胞迁移能力。这些发现不仅为AS调控CRC的机制提供了新的见解,也为CRC的靶向剪接治疗提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b433/11247070/c3bc7676fe23/12672_2024_1149_Fig1_HTML.jpg

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