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MicroRNA-125b exerts antitumor functions in cutaneous squamous cell carcinoma by targeting the STAT3 pathway

Ke Tian1, Wanggen Liu2, Jing Zhang3

  • 11Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan, 056002 China.

Cellular & Molecular Biology Letters
|March 13, 2020
PubMed
Abstract

Insights

MicroRNA-125b (miR-125b) suppresses cutaneous squamous cell carcinoma (CSCC) by targeting the STAT3 pathway. Restoring miR-125b levels may offer a novel therapeutic strategy for CSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNA-125b (miR-125b) is downregulated in human cutaneous squamous cell carcinoma (CSCC).
  • The precise function of miR-125b in CSCC pathogenesis remains incompletely understood.
  • The interaction between miR-125b and signal transducer and activator of transcription 3 (STAT3) in CSCC requires further investigation.

Purpose of the Study:

  • To elucidate the functional role of miR-125b in CSCC.
  • To investigate the regulatory relationship between miR-125b and STAT3 in CSCC.
  • To determine the impact of the miR-125b-STAT3 axis on CSCC cell behavior.

Main Methods:

  • Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting to assess expression levels of the miR-125b-STAT3 axis.
  • Luciferase reporter gene assays and RNA immunoprecipitation (RIP) to confirm direct targeting of STAT3 by miR-125b.
  • MTT assays and flow cytometry to evaluate the effects of modulating the miR-125b-STAT3 axis on CSCC cell proliferation and apoptosis.

Main Results:

  • Significantly lower miR-125b expression and higher STAT3 expression were observed in CSCC tissues and cell lines compared to normal controls.
  • miR-125b was confirmed to directly target and downregulate STAT3 expression.
  • Overexpression of miR-125b suppressed CSCC cell proliferation and induced apoptosis, partly through the downregulation of STAT3, Cyclin D1, and Bcl2.

Conclusions:

  • miR-125b functions as a tumor suppressor in CSCC by inhibiting the STAT3 signaling pathway.
  • The miR-125b-STAT3 axis represents a critical molecular mechanism in CSCC development.
  • Targeting miR-125b activation or STAT3 inhibition presents a promising therapeutic avenue for CSCC.
Keywords:
Cutaneous squamous cell carcinomaSignal transducer and activator of transcription (STAT) 3microRNA-125b

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