Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth

Peng Ru, Peng Hu, Feng Geng, Xiaokui Mo, Chunming Cheng, Ji Young Yoo, Xiang Cheng, Xiaoning Wu, Jeffrey Yunhua Guo, Ichiro Nakano, Etienne Lefai, Balveen Kaur, Arnab Chakravarti, Deliang Guo

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Dysregulated lipid metabolism is a characteristic of malignancies. Sterol regulatory element binding protein 1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is highly activated in malignancies. Here, we unraveled a link between miR-29 and the SCAP (SREBP cleavage-activating protein)/SREBP-1 pathway in glioblastoma (GBM) growth. Epidermal growth factor receptor (EGFR) signaling enhances miR-29 expression in GBM cells via upregulation of SCAP/SREBP-1, and SREBP-1 activates miR-29 expression via binding to specific sites in its promoter. In turn, miR-29 inhibits SCAP and SREBP-1 expression by interacting with their 3′ UTRs. miR-29 transfection suppressed lipid synthesis and GBM cell growth, which were rescued by the addition of fatty acids or N-terminal SREBP-1 expression. Xenograft studies showed that miR-29 mimics significantly inhibit GBM growth and prolong the survival of GBM-bearing mice. Our study reveals a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling mediated by miR-29 and suggests that miR-29 treatment may represent an effective means to target GBM.

Original languageEnglish (US)
Pages (from-to)1527-1535
Number of pages9
JournalCell Reports
Issue number6
StatePublished - Aug 9 2016
Externally publishedYes


  • EGFR
  • SCAP
  • SREBP-1
  • glioblastoma
  • lipid metabolism
  • miR-29

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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