CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma

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• 作者：You-ke Xie (12) xieyouke@163.com
  Shao-fen Huo (1) huoshaofen@gmail.com
  Gong Zhang (3) zhanggong7446@163.com
  Fu Zhang (4) coronerzhang@yahoo.com.cn
  Zu-ping Lian (2) zupinglian@sina.com
  Xiong-lin Tang (5) bearnone@163.com
  Chuan Jin (6) jinchuanmed@163.com
• 关键词：CDA ; 2 – ; miR ; 124 – ; SLUG – ; Twist – ; Glioma
• 刊名：Journal of Neuro-Oncology
• 出版年：2012
• 出版时间：November 2012
• 年：2012
• 卷：110
• 期：2
• 页码：179-186
• 全文大小：524.0 KB
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• 作者单位：1. Cancer Research Institute of Southern Medical University, Guangzhou, 510515 People鈥檚 Republic of China2. Ruikang Hospital of Guangxi Traditional Chinese Medical University, Nanning, 530011 People鈥檚 Republic of China3. Department of Radiotherapy of People鈥檚 Hospital of Shanxi Province, Taiyuan, 030000 People鈥檚 Republic of China4. Forensic Medicine Institute of Southern Medical University, Guangzhou, 510515 People鈥檚 Republic of China5. Nerve Internal Medicine Department of Affiliated Hospital, Youjiang Medical University for Nationalities, Baise, 533000 People鈥檚 Republic of China6. Internal Medical Department of Guangzhou Medical University Cancer Institute and Hospital, Guangzhou, 510182 People鈥檚 Republic of China
• ISSN：1573-7373

文摘

Cell differentiation agent-2 (CDA-2) is an extraction from healthy human urine consisting of primary organic acids and peptides, and it has been demonstrated to inhibit growth and induce differentiation in glioma and other cell lines. But the mechanism of CDA-2 remains unclear. In this study, we demonstrated that CDA-2 inhibited cell growth and induced differentiation of glioma cells, accompanied with decreased expression of SLUG, Twist and Vimentin in both SWO-38 and U251 cell lines. Overexpression of SLUG or Twist greatly eliminated the efficiency of CDA-2 in inducing differentiation. Further study showed that CDA-2 treatment resulted in great changed microRNAs (miRNAs) detected by quantitative PCR, in which miR-124 was one of the most changed miRNAs and its level was increased by fourfold. The result of miRNA target prediction showed that miR-124 could regulate hundreds of genes which were relative to cell differentiation, such as SLUG, Vimentin, actin cytoskeleton, focal adhesion, tight junction. Inhibition of miR-124 up-regulated SLUG, Twist and Vimentin proteins, and partly eliminated the function of CDA-2 on these mesenchymal markers. Our findings demonstrated for the first time that CDA-2 induced cell differentiation through suppressing Twist and SLUG via miR-124 in glioma cells.