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

富含丝氨酸/丝氨酸的剪接因子3（Serine/cytosine-rich splicing factor 3，SRSF 3）是SRSF家族的一员，在基因表达中起着广泛的作用。SRSF 3基因敲低可诱导结肠癌细胞（HCT 116）的G1期阻滞和凋亡。在SRSF 3沉默细胞中差异表达的转录本和与过表达的SRSF 3免疫沉淀的mRNA的通路分析表明，SRSF 3优先与G1/S检查点调节器mRNA相关并调节其表达。SRSF 3敲低降低了细胞周期蛋白（D1、D3和E1）、E2 F1和E2 F7的mRNA和蛋白水平。SRSF 3敲低导致hipk 2外显子8的81个核苷酸跳读。产生的HIPK 2亚型部分缺乏E3泛素连接酶结合位点变得对蛋白酶体消化有抗性。在表达野生型或突变型p53的各种结肠癌细胞中，通过选择性分解全长hipk 2 mRNA以及通过SERF 3敲低诱导的剪接变体的优势表达诱导细胞凋亡。

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.