SRSF1 Prevents DNA Damage and Promotes Tumorigenesis through Regulation of DBF4B Pre-mRNA Splicing | Zendy

Linlin Chen | Zendy; Chunling Luo | Zendy; Lei Shen | Zendy; Yuguo Liu | Zendy; Qianqian Wang | Zendy; Chang Zhang | Zendy; Ruochen Guo | Zendy; Yanan Zhang | Zendy; Zhiqin Xie | Zendy; Ning Wei | Zendy; Wenwu Wu | Zendy; Jun Han | Zendy; Ying Feng | Zendy

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SRSF1 Prevents DNA Damage and Promotes Tumorigenesis through Regulation of DBF4B Pre-mRNA Splicing

Author(s) -

Linlin Chen,

Chunling Luo,

Lei Shen,

Yuguo Liu,

Qianqian Wang,

Chang Zhang,

Ruochen Guo,

Yanan Zhang,

Zhiqin Xie,

Ning Wei,

Wenwu Wu,

Jun Han,

Ying Feng

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.11.091

Subject(s) - rna splicing , gene knockdown , alternative splicing , splicing factor , carcinogenesis , biology , phenocopy , cancer research , downregulation and upregulation , dna damage , genome instability , rna binding protein , microbiology and biotechnology , messenger rna , cancer , phenotype , genetics , rna , gene , dna

Dysregulated alternative splicing events have been implicated in many types of cancer, but the underlying molecular mechanisms remain unclear. Here, we observe that the splicing factor SRSF1 regulates DBF4B exon6 splicing by specifically binding and promoting its inclusion. Knockdown of the exon6-containing isoform (DBF4B-FL) significantly inhibits the tumorigenic potential of colon cancer cells in vitro and in mice, and SRSF1 inactivation phenocopies DBF4B-FL depletion. DBF4B-FL and SRSF1 are required for cancer cell proliferation and for the maintenance of genomic stability. Overexpression of DBF4B-FL can protect against DNA damage induced by SRSF1 knockdown and rescues growth defects in SRSF1-depleted cells. Increased DBF4B exon6 inclusion parallels SRSF1 upregulation in clinical colorectal cancer samples. Taken together, our findings identify SRSF1 as a key regulator of DBF4B pre-mRNA splicing dysregulation in colon cancer, with possible clinical implications as candidate prognostic factors in cancer patients.

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