title: Serine/arginine-rich splicing factor 7 regulates p21-dependent growth arrest in colon cancer cells.
abstract: Serine/arginine-rich splicing factors (SRSFs) play wide-ranging roles in gene expression through post-transcriptional regulation as well as pre-mRNA splicing. SRSF7 was highly expressed in colon cancer tissues, and its knockdown inhibited cell growth in colon cancer cells (HCT116) in association with altered expression of 4,499 genes. The Ingenuity Pathway Analysis revealed that cell cycle-related canonical pathways were ranked as the highly enriched category in the affected genes. Western blotting confirmed that p21, a master regulator in cell cycle, was increased without any induction of p53 in SRSF7 knockdown cells. Furthermore, cyclin-dependent kinase 2 and retinoblastoma protein were remained in the hypophosphorylated state. In addition, the SRSF7 knockdown-induced cell growth inhibition was observed in p53-null HCT116 cells, suggesting that p53-independent pathways were involved in the SRSF7 knockdown-induced cell growth inhibition. The reduction of SRSF7 stabilized cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA without any activation of the CDKN1A promoter. Interestingly, SRSF7 knockdown also blocked p21 degradation. These results suggest that the reduction of SRSF7 post-transcriptionally regulates p21 induction at the multistep processes. Thus, the present findings disclose a novel, important role of SRSF7 in cell proliferation through regulating p21 levels. J. Med. Invest. 63: 219-226, August, 2016.
authors.affiliation: Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Saki
authors.initials: S
authors.lastname: Saijo
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuwano
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Masuda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Rokutan
authors.forename: Kensei
authors.initials: K
authors.lastname: Nishida
mesh_terms: D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D000068103:Serine-Arginine Splicing Factors / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; C000595780:SRSF7 protein, human; D016159:Tumor Suppressor Protein p53; D000068103:Serine-Arginine Splicing Factors