Splicing factor SRSF3 promotes the progression of cervical cancer through regulating DDX5. Issue 2 (25th October 2022)

• Record Type: Journal Article
• Authors: Che, Yingying; Bai, Mixue; Lu, Kun; Fu, Lin
• Is Part Of: Molecular carcinogenesis. Volume 62:Issue 2(2023)
• Page Start: 210
• Page End: 223
• Publication Date: 2022-10-25
• Subjects: AKT -- alternative splicing -- cervical carcinoma -- DDX5 -- SRSF3; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.23477
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract: Aberrant alternative splicing (AS) profoundly affects tumorigenesis and cancer progression. Serine/arginine‐rich splicing factor 3 (SRSF3) regulates the AS of precursor mRNAs and acts as a proto‐oncogene in many tumors, but its function and potential mechanisms in cervical cancer remain unclear. Here, we found that SRSF3 was highly expressed in cervical cancer tissues and that SRSF3 expression was correlated with prognosis after analyses of the The Cancer Genome Atlas and GEO databases. Furthermore, knockdown of SRSF3 reduced the proliferation, migration, and invasion abilities of HeLa cells, while overexpression of SRSF3 promoted proliferation, migration, and invasion of CaSki cells. Further studies showed that SRSF3 mediated the variable splicing of exon 12 of the transcriptional cofactor DEAD‐box helicase 5 (DDX5). Specifically, overexpression of SRSF3 promoted the production of the pro‐oncogenic spliceosome DDX5‐L and repressed the production of the repressive spliceosome DDX5‐S. Ultimately, both SRSF3 and DDX5‐L were able to upregulate oncogenic AKT expression, while DDX5‐S downregulated AKT expression. In conclusion, we found that SRSF3 increased the production of DDX5‐L and decreased the production of DDX5‐S by regulating the variable splicing of DDX5. This, in turn promoted the proliferation, migration, and invasion of cervical cancer by upregulating the expression level of AKT. These results reveal the oncogenic role of SRSF3 in cervical cancer and emphasize the importance of the SRSF3‐DDX5‐AKT axis in tumorigenesis. SRSF3 and DDX5 are new potential biomarkers and therapeutic targets for cervical cancer.