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Published on: July 22, 2020
SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30
Ji-Lin Wang1, Chun-Rong Guo2, Tian-Tian Sun1
11Division 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.
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.
Insights
SRSF3, a splicing factor, is overexpressed in colorectal cancer (CRC) and drives tumor progression by regulating ArhGAP30/Ace-p53. Targeting SRSF3 offers potential prognostic and therapeutic strategies for CRC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The splicing factor SRSF3 is an oncogene implicated in various cancers.
- Its specific role and mechanism in colorectal cancer (CRC) progression were previously unclear.
Purpose of the Study:
- To investigate the relationship between SRSF3 and the carcinogenesis and progression of CRC.
- To elucidate the functional mechanism of SRSF3 in CRC development.
Main Methods:
- Immunohistochemistry was used to detect SRSF3 expression in CRC tissues.
- Cell proliferation, invasion, and survival were assessed using CCK-8, colony formation, and transwell assays.
- Gene expression was analyzed via Western blot and real-time PCR; xenograft experiments evaluated in vivo tumor growth.
Main Results:
- SRSF3 was overexpressed in CRC tissues, correlating with poor differentiation, lymph node invasion, and advanced AJCC stage.
- High SRSF3 expression was linked to shorter overall survival.
- SRSF3 knockdown suppressed CRC cell proliferation, migration, and survival by activating ArhGAP30/Ace-p53; conversely, SRSF3 overexpression promoted these processes.
- In vivo targeting of SRSF3 inhibited tumor progression in xenograft models.
Conclusions:
- SRSF3 acts as a key regulator of the ArhGAP30/Ace-p53 pathway in CRC.
- SRSF3 demonstrates significant prognostic and therapeutic potential for colorectal cancer.
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