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

富丝氨酸/精氨酸剪接因子3 （SRSF3）是SRSF家族的一员，在基因表达中起着广泛的作用。SRSF3敲低诱导结肠癌细胞G1阻滞和凋亡（HCT116）。对SRSF3沉默细胞和过表达SRSF3免疫沉淀mrna中差异表达转录物的通路分析表明，SRSF3优先与G1/S检查点调节mrna相关并调节其表达。SRSF3敲除降低细胞周期蛋白（D1、D3和E1）、E2F1和E2F7的mRNA和蛋白水平。SRSF3敲除导致hipk2外显子8的81个核苷酸跳跃。由此产生的HIPK2异构体部分缺乏E3泛素连接酶结合位点，对蛋白酶体消化产生抗性。在多种表达野生型或突变型p53的结肠癌细胞中，通过选择性分解全长hipk2 mRNA和敲低SERF3诱导凋亡的剪接变异体的主要表达。

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.