MicroRNA-21 deficiency suppresses prostate cancer progression through downregulation of the IRS1-SREBP-1 signaling pathway

Thanigaivelan Kanagasabai, Guoliang Li, Tian Huai Shen, Nataliya Gladoun, Mireia Castillo-Martin, Sherly I. Celada, Yingqiu Xie, Lakendria K. Brown, Zaniya A. Mark, Josiah Ochieng, Billy R. Ballard, Carlos Cordon-Cardo, Samuel E. Adunyah, Renjie Jin, Robert J. Matusik, Zhenbang Chen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor in lipogenesis and lipid metabolism, is critical for disease progression and associated with poor outcomes in prostate cancer (PCa) patients. However, the mechanism of SREBP-1 regulation in PCa remains elusive. Here, we report that SREBP-1 is transcriptionally regulated by microRNA-21 (miR-21) in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of SREBP-1, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) in Pten/Trp53 double-null mouse embryonic fibroblasts (MEFs) and Pten/Trp53 double-null mutant mice. Strikingly, miR-21 loss significantly reduced cell proliferation and suppressed the prostate tumorigenesis of Pten/Trp53 mutant mice. Mechanistically, miR-21 inactivation decreased the levels of SREBP-1, FASN, and ACC in human PCa cells through downregulation of insulin receptor substrate 1 (IRS1)-mediated transcription and induction of cellular senescence. Conversely, miR-21 overexpression increased cell proliferation and migration; as well as the levels of IRS1, SREBP-1, FASN, and ACC in human PCa cells. Our findings reveal that miR-21 promotes PCa progression by activating the IRS1/SREBP-1 axis, and targeting miR-21/SREBP-1 signaling pathway can be a novel strategy for controlling PCa malignancy.

Original languageEnglish
Pages (from-to)46-54
Number of pages9
JournalCancer Letters
StatePublished - 28 Jan 2022
Externally publishedYes


  • ACC
  • FASN
  • Fatty acid signaling and mouse models
  • PTEN
  • TP53


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