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

  • Laboratory Investigation
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Abstract

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.

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Acknowledgments

This research was supported by Foundation of Science and Technology Department of Guangdong Province, China (No. 2011B080701021).

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Authors and Affiliations

  1. Cancer Research Institute of Southern Medical University, Guangzhou, 510515, People’s Republic of China

    You-ke Xie & Shao-fen Huo

  2. Ruikang Hospital of Guangxi Traditional Chinese Medical University, Nanning, 530011, People’s Republic of China

    You-ke Xie & Zu-ping Lian

  3. Department of Radiotherapy of People’s Hospital of Shanxi Province, Taiyuan, 030000, People’s Republic of China

    Gong Zhang

  4. Forensic Medicine Institute of Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Fu Zhang

  5. Nerve Internal Medicine Department of Affiliated Hospital, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China

    Xiong-lin Tang

  6. Internal Medical Department of Guangzhou Medical University Cancer Institute and Hospital, Guangzhou, 510182, People’s Republic of China

    Chuan Jin

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  1. You-ke Xie
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Correspondence to Chuan Jin.

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You-ke Xie, Shao-fen Huo, Gong Zhang, and Fu Zhang contributed equally to this study.

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Xie, Yk., Huo, Sf., Zhang, G. et al. CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma. J Neurooncol 110, 179–186 (2012). https://doi.org/10.1007/s11060-012-0961-x

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  • DOI: https://doi.org/10.1007/s11060-012-0961-x

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