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A negative feedback regulatory loop between miR-138 and TP53 is mediated by USP10

Zhenghua Luo1, Manchao Zhang1, Ri Cui1

  • 1Department of Cancer Biology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.

Oncotarget
|November 8, 2019
PubMed

Insights

MicroRNA-138 regulates the tumor suppressor TP53 by targeting USP10. A feedback loop exists where TP53 represses microRNA-138, adding complexity to cancer gene networks.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • TP53 is a crucial tumor suppressor gene, frequently altered in human cancers.
  • TP53 expression is tightly regulated by pathways including Mdm2-mediated ubiquitination and deubiquitination by USP7 and USP10.
  • MicroRNAs play roles in regulating TP53 levels and function.

Purpose of the Study:

  • To investigate the role of microRNA-138 in regulating TP53.
  • To elucidate the regulatory mechanism involving microRNA-138, TP53, and USP10.

Main Methods:

  • Investigated microRNA-138's direct targeting of USP10.
  • Analyzed the feedback loop between TP53 and microRNA-138 expression.

Main Results:

  • MicroRNA-138 directly targets and regulates USP10.
  • TP53 was found to repress microRNA-138 expression.
  • A negative feedback regulatory loop between TP53 and microRNA-138 was identified.

Conclusions:

  • MicroRNA-138 acts as a regulator of TP53 by targeting USP10.
  • The discovered negative feedback loop adds complexity to the TP53 regulatory network in cancer.
Keywords:
TP53USP10miR-138

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