SRSF3通过调节ArhGAP30的表达在结直肠癌中发挥癌基因的作用。
SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30.
作者信息
Wang Ji-Lin, Guo Chun-Rong, Sun Tian-Tian, Su Wen-Yu, Hu Qiang, Guo Fang-Fang, Liang Lun-Xi, Xu Jie, Xiong Hua, Fang Jing-Yuan
机构信息
1Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai, 200001 China.
2The Centre of Teaching and Experiment, Shanghai University of Traditional Chinese Medicine, Pudong District, Shanghai, China.
出版信息
Cancer Cell Int. 2020 Apr 10;20:120. doi: 10.1186/s12935-020-01201-2. eCollection 2020.
BACKGROUND
Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC.
METHODS
The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR.
RESULTS
SRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo.
CONCLUSIONS
Taken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.
背景
剪接因子SRSF3是一种癌基因，在多种癌症中过表达，然而，其在结直肠癌（CRC）中的功能及机制仍不清楚。本研究旨在探讨SRSF3与CRC发生发展之间的关系。
方法
采用免疫组织化学法检测CRC组织中SRSF3的表达。通过CCK-8法、集落形成试验、Transwell侵袭试验和异种移植实验分析细胞增殖和侵袭率。采用蛋白质免疫印迹法或实时荧光定量PCR检测相关基因的表达。
结果
SRSF3在CRC组织中过表达，其高表达与CRC分化、淋巴结转移及美国癌症联合委员会（AJCC）分期有关。SRSF3上调还与总生存期缩短有关。敲低CRC细胞中的SRSF3可激活ArhGAP30/Ace-p53，降低细胞增殖、迁移和存活率；而SRSF3的异位表达则减弱ArhGAP30/Ace-p53，增加细胞增殖、迁移和存活率。在异种移植瘤中靶向SRSF3可抑制体内肿瘤进展。
结论
综上所述，我们的数据确定SRSF3是CRC中ArhGAP30/Ace-p53的调节因子，并突出了SRSF3在CRC中的潜在预后和治疗意义。
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