Oncogene SRSF3 suppresses autophagy via inhibiting BECN1 expression

• Published in: Biochemical and biophysical research communications 2019-02, Vol.509 (4), p.966-972
• Main Authors: Zhou, Lu, Guo, Jihua, Jia, Rong
• Format: Article
• Language: English
• Subjects: Autophagy; BECN1; SRSF3
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.01.048

Autophagy is an evolutionarily conserved cellular catabolic process. Dysfunction in the autophagy pathway has been demonstrated to be associated with many human diseases, including cancer. Alternative splicing of pre-mRNA is also an evolutionarily conserved regulatory mechanism of gene expression. Dysregulation of alternative splicing is increasingly linked to cancer. However, the association between these two cellular conserved processes is unclear. Splicing factors are critical players in the regulation of alternative splicing of pre-mRNA. We analyzed the expression of 28 splicing factors during hypoxia-induced autophagy in three oral squamous cell carcinoma (OSCC) cell lines. We discovered that oncogenes SRSF3 and SRSF1 are significantly downregulated in all three cell lines. Moreover, knockdown of SRSF3 increased autophagic activity, whereas overexpression of SRSF3 inhibited hypoxia-induced autophagy. Loss-of-function and gain-of-function assays also showed that SRSF3 inhibits the expression of p65 and FoxO1 and their downstream target gene BECN1, a key regulator of autophagy. Our results demonstrated that splicing factor SRSF3 is an autophagy suppressor. •Oncogenic splicing factor SRSF3 inhibits autophagy in oral cancer cells.•SRSF3 inhibits the expression of BECN1, a key mediator of autophagy.•SRSF3 inhibits the expression of BECN1 via downregulating p65 and FoxO1.