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

Cell Mol Biol Lett. 2020 Mar 5:25:12. doi: 10.1186/s11658-020-00207-y. eCollection 2020.

Abstract

Background: MicroRNA-125b (miR-125b) is downregulated in human cutaneous squamous cell carcinoma (CSCC). However, its function in CSCC has yet to be extensively explored. Here, we analyze the relationship between signal transducer and activator of transcription 3 (STAT3) and miR-125b in CSCC.

Methods: Western blotting and quantitative RT-PCR were used to determine the expression of the miR-125b-STAT3 axis in human CSCC tissues and cell lines. The direct regulatory effect of miR-125b on STAT3 expression was assessed using a luciferase reporter gene assay and RNA immunoprecipitation assay. The MTT assay and flow cytometry were used to determine the role of the miR-125b-STAT3 axis in CSCC cell proliferation and apoptosis.

Results: MiR-125b expression levels were significantly lower in CSCC cell lines and tissues than in normal cell lines and tissues. STAT3 was identified as the direct target of miR-125b. Upregulation of miR-125b and downregulation of STAT3 suppressed cell proliferation and promoted cell apoptosis. Cyclin D1 and Bcl2 were identified as the downstream targets of the miR-125-STAT3 axis.

Conclusions: Our findings indicate that miR-125b acts as a tumor suppressor in CSCC by targeting the STAT3 pathway. This observation increases our understanding of the molecular mechanisms of CSCC. Therapies aimed at activating miR-125b or inhibiting STAT3 signaling should be explored as potential treatments for CSCC.

Keywords: Cutaneous squamous cell carcinoma; Signal transducer and activator of transcription (STAT) 3; microRNA-125b.

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin D1 / metabolism
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / genetics
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*

Substances

  • BCL2 protein, human
  • MIRN125 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Cyclin D1