Serine/arginine-rich splicing factor 7 regulates p21-dependent growth arrest in colon cancer cells

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Author(s)

    • Saijo Saki
    • Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Kuwano Yuki
    • Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Masuda Kiyoshi
    • Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Nishikawa Tatsuya
    • Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Rokutan Kazuhito
    • Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Nishida Kensei
    • Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School

Abstract

<p>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 <i>cyclin-dependent kinase inhibitor 1A</i> (<i>CDKN1A</i>) mRNA without any activation of the <i>CDKN1A</i> 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</p>

Journal

  • The Journal of Medical Investigation

    The Journal of Medical Investigation 63(3.4), 219-226, 2016

    The University of Tokushima Faculty of Medicine

Codes

  • NII Article ID (NAID)
    130005245836
  • NII NACSIS-CAT ID (NCID)
    AA11166929
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1343-1420
  • Data Source
    IR  J-STAGE 
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