MiR-148a inhibits oral squamous cell carcinoma progression through ERK/MAPK pathway via targeting IGF-IR

Biosci Rep. 2020 Apr 30;40(4):BSR20182458. doi: 10.1042/BSR20182458.

Abstract

Objective: The current study aimed to investigate the functional roles and clinical significance of microRNA-148a (miR-148a) in the progression of oral squamous cell carcinoma (OSCC).

Methods: Relative expression of miR-148a in OSCC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was performed to estimate the relationship between miR-148a expression and clinical characteristics of OSCC patients. Cell transfection was carried out using Lipofectamine® 2000. Biological behaviors of tumor cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays. Bioinformatics analysis and luciferase reporter assay were used to identify the target genes of miR-148a. Protein expression was detected through Western blot analysis.

Results: MiR-148a expression was obviously decreased in OSCC tissues and cells, and such down-regulation was closely correlated with lymph node metastasis (P=0.027) and tumor node metastasis (TNM) stage (P=0.001) of OSCC patients. miR-148a overexpression could significantly impair OSCC cell proliferation, migration and invasion in vitro (P<0.05 for all). Insulin-like growth factor-I receptor (IGF-IR) was a potential target of miR-148a. MiR-148a could inhibit ERK/MAPK signaling pathway through targeting IGF-IR.

Conclusion: MiR-148a plays an anti-tumor role in OSCC and inhibits OSCC progression through suppressing ERK/MAPK pathway via targeting IGF-IR.

Keywords: ERK/MAPK pathway; IGF-IR; MiR-148a; MicroRNA; Oral squamous cell carcinoma.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis / genetics*
  • MAP Kinase Signaling System / genetics
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Receptor, IGF Type 1 / genetics*
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • IGF1R protein, human
  • MIRN148 microRNA, human
  • MicroRNAs
  • Receptor, IGF Type 1