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Negative regulation of miR-145 by C/EBP-β through the Akt pathway in cancer cells

Mohit Sachdeva1, Qian Liu, Julia Cao

  • 1Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.

Nucleic Acids Research
|April 13, 2012
PubMed

Insights

CCAAT/enhancer binding protein beta (C/EBP-β) suppresses tumor suppressor miR-145 expression by binding its promoter. This C/EBP-β regulation of miR-145 is independent of p53 and may explain miR-145 downregulation in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) are key gene regulators, with miR-145 acting as a tumor suppressor by silencing c-Myc.
  • The tumor suppressor p53 induces miR-145, establishing its role in p53-mediated c-Myc repression.
  • The reasons for miR-145 downregulation in tumors remain largely unknown.

Purpose of the Study:

  • To identify factors responsible for miR-145 downregulation in cancer.
  • To investigate the regulatory role of CCAAT/enhancer binding protein beta (C/EBP-β) on miR-145 expression.
  • To elucidate the relationship between C/EBP-β, p53, and miR-145 in cancer cells.

Main Methods:

  • Promoter binding assays to assess C/EBP-β interaction with the miR-145 promoter.
  • Analysis of miR-145 expression in the presence of wild-type and mutant p53 with varying C/EBP-β levels.
  • Investigating the effect of resveratrol on Akt, C/EBP-β phosphorylation, and miR-145 expression.

Main Results:

  • CCAAT/enhancer binding protein beta (C/EBP-β) directly binds to the miR-145 promoter, acting as a negative regulator.
  • C/EBP-β suppresses miR-145 expression independently of p53 status, counteracting p53-induced miR-145.
  • Both large (LAP-2) and small (LIP) isoforms of C/EBP-β suppress miR-145; resveratrol induces miR-145 by inhibiting Akt and C/EBP-β phosphorylation.

Conclusions:

  • C/EBP-β is a novel negative regulator of miR-145.
  • A regulatory network involving Akt, C/EBP-β, and miR-145 is identified.
  • This pathway may contribute to the observed downregulation of miR-145 in various cancers.

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