Downregulation o fserine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells

富含丝氨酸/精氨酸的剪接因子3(SRSF3)是SRSF家族中的一个成员，在基因表达中发挥着广泛的作用。SRSF3基因敲除可诱导结肠癌细胞(HCT116)G1期停滞和凋亡。对SRSF3沉默细胞和过表达SRSF3免疫沉淀中差异表达的转录本的通径分析表明，SRSF3优先与G1/S检查点调节因子mRNAs结合并调控其表达。SRSF3基因敲除降低了细胞周期蛋白(d1、d3和e1)、E2F1和E2F7的mRNA和蛋白水平。SRSF3基因敲除导致HIPK2外显子8的81个核苷酸被跳过。由此产生的HIPK2亚型部分缺乏E3泛素连接酶结合位点，对蛋白酶体消化产生抵抗力。剪接变异体的优势表达通过选择性分解全长Hipk2 mRNA以及通过SERF3敲除诱导表达野生型或突变型P53的各种结肠癌细胞的凋亡。

Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SRSF family that plays wide-ranging roles in gene expression. SRSF3 knockdown induced G1 arrest and apoptosis in colon cancer cells (HCT116). Pathway analysis of differentially expressed transcripts in SRSF3-silenced cells and mRNAs immunoprecipitated with overexpressed SRSF3 suggested that SRSF3 preferentially associated with G1/S checkpoint regulator mRNAs and regulated their expression. SRSF3 knockdown decreased mRNA and protein levels of cyclins (D1, D3, and E1), E2F1, and E2F7. SRSF3 knockdown caused skipping of 81 nucleotides of the hipk2 exon 8. Resultant HIPK2 isoform partially lacking the E3 ubiquitin ligase-binding site became resistant to proteasome digestion. Predominant expression of the splice variant by selective decomposition of full-length hipk2 mRNA as well as by SERF3 knockdown induced apoptosis in a variety of colon cancer cells expressing wild-type or mutated p53.