SRSF2 Regulates Alternative Splicing to Drive Hepatocellular Carcinoma Development.

Abstract

Aberrant RNA splicing is recognized to contribute to cancer pathogenesis, but the underlying mechanisms remain mainly obscure. Here, we report that the splicing factor SRSF2 is upregulated frequently in human hepatocellular carcinoma (HCC), where this event is associated with poor prognosis in patients. RNA-seq and other molecular analyses were used to identify SRSF2-regulated alternative splicing events. SRSF2 binding within an alternative exon was associated with its inclusion in the RNA, whereas SRSF2 binding in a flanking constitutive exon was associated with exclusion of the alternative exon. Notably, cancer-associated splice variants upregulated by SRSF2 in clinical specimens of HCC were found to be crucial for pathogenesis and progression in hepatoma cells, where SRSF2 expression increased cell proliferation and tumorigenic potential by controlling expression of these variants. Our findings identify SRSF2 as a key regulator of RNA splicing dysregulation in cancer, with possible clinical implications as a candidate prognostic factor in patients with HCC. Cancer Res; 77(5); 1168-78. ©2017 AACR.

• Authors: Chunling Luo, Yuanming Cheng, Yuguo Liu, Linlin Chen, Lina Liu, Ning Wei, Zhiqin Xie, Wenwu Wu, Ying Feng
• Journal: Cancer research (Cancer Res) Vol. 77 Issue 5 Pg. 1168-1178 (03 01 2017) ISSN: 1538-7445 [Electronic] United States
• PMID: 28082404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• SRSF2 protein, human
• Serine-Arginine Splicing Factors

Topics

• Alternative Splicing
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Line, Tumor
• HEK293 Cells
• Humans
• Liver Neoplasms (genetics, pathology)
• Serine-Arginine Splicing Factors (genetics)
• Transfection