期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 429, 期 3-4, 页码 173-179出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.10.117
关键词
miRNA; Protein kinase CKII; Senescence; p53; Reactive oxygen species; Cancer cells
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2010-0024102]
- Kyungpook National University
- National Research Foundation of Korea [2010-0024102] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
We previously demonstrated that downregulation of protein kinase CKII induces cellular senescence in human colon cancer HCT116 cells. To investigate the role of microRNAs (miRNAs) in CKII downregulation during senescence, we employed computational algorithms. Four miRNAs (miR-186, miR-216b, miR-337-3p. and miR-760) were predicted to be miRNAs against CKII alpha mRNA. Mimics of all four miRNAs jointly downregulated CKII alpha expression in HCT116 cells. Reporter analysis and RT-PCR have suggested that these four miRNAs may stimulate degradation of CKII alpha mRNA by targeting its 3' untranslated regions (UTRs). The four miRNA mimics increased senescent-associated beta-galactosidase (SA-beta-gal) staining, p53 and p21(Cip1/WAF1) expression, and reactive oxygen species (ROS) production. In contrast, concomitant knockdown of the four miRNAs by antisense inhibitors increased the CKII alpha protein level and suppressed CKII inhibition-mediated senescence. Finally, CKII alpha overexpression antagonized senescence induced by the four miRNA mimics. Therefore, the present results show that miR-186, miR-216b, miR-337-3p, and miR-760 cooperatively promote cellular senescence through the p53-p21(Cip1/WAF1) pathway by CKII downregulation-mediated ROS production in HCT116 cells. (C) 2012 Elsevier Inc. All rights reserved.
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