SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30

Ji-Lin Wang; Chun-Rong Guo; Tian-Tian Sun; Wen-Yu Su; Qiang Hu; Fang-Fang Guo; Lun-Xi Liang; Jie Xu; Hua Xiong; Jing-Yuan Fang

doi:10.1186/s12935-020-01201-2

SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30

Cancer Cell Int. 2020 Apr 10:20:120. doi: 10.1186/s12935-020-01201-2. eCollection 2020.

Authors

Ji-Lin Wang^#¹, Chun-Rong Guo^#², Tian-Tian Sun¹, Wen-Yu Su¹, Qiang Hu¹, Fang-Fang Guo¹, Lun-Xi Liang¹, Jie Xu¹, Hua Xiong¹, Jing-Yuan Fang¹

Affiliations

¹ 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.
² 2The Centre of Teaching and Experiment, Shanghai University of Traditional Chinese Medicine, Pudong District, Shanghai, China.

^# Contributed equally.

Abstract

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.

Keywords: ArhGAP30; Colorectal cancer; SRSF3.