Journal of Neuro-Oncology

, Volume 110, Issue 2, pp 179–186 | Cite as

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

  • You-ke Xie
  • Shao-fen Huo
  • Gong Zhang
  • Fu Zhang
  • Zu-ping Lian
  • Xiong-lin Tang
  • Chuan Jin
Laboratory Investigation


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.


CDA-2 miR-124 SLUG Twist Glioma 



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


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • You-ke Xie
    • 1
    • 2
  • Shao-fen Huo
    • 1
  • Gong Zhang
    • 3
  • Fu Zhang
    • 4
  • Zu-ping Lian
    • 2
  • Xiong-lin Tang
    • 5
  • Chuan Jin
    • 6
  1. 1.Cancer Research Institute of Southern Medical UniversityGuangzhouPeople’s Republic of China
  2. 2.Ruikang Hospital of Guangxi Traditional Chinese Medical UniversityNanningPeople’s Republic of China
  3. 3.Department of Radiotherapy of People’s Hospital of Shanxi ProvinceTaiyuanPeople’s Republic of China
  4. 4.Forensic Medicine Institute of Southern Medical UniversityGuangzhouPeople’s Republic of China
  5. 5.Nerve Internal Medicine Department of Affiliated HospitalYoujiang Medical University for NationalitiesBaisePeople’s Republic of China
  6. 6.Internal Medical Department of Guangzhou Medical University Cancer Institute and HospitalGuangzhouPeople’s Republic of China

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