Inhibition of miR-133b indicates poor prognosis and promotes progression of OSCC via SOX4

Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12717-12726. doi: 10.26355/eurrev_202012_24170.

Abstract

Objective: Oral squamous cell carcinoma (OSCC) accounts for the first largest proportion of oral and maxillofacial malignancies worldwide. Increasing studies have indicated that miRNAs are involved in the regulation of various tumors, including OSCC. However, the exact role of miR-133b in OSCC has not been fully elucidated. Here, we aimed to explore the effects of miR-133b on the development and progression of OSCC and its related mechanisms.

Patients and methods: Expression of miR-133b in 44 paired OSCC tissues and adjacent normal tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Clinicopathological characteristics were collected from OSCC patients, and the relationship between miR-133b expression and the prognosis of patients was analyzed. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and colony formation assays were employed to measure the proliferation of OSCC cells transfected with miR-133b inhibitors or mimics. Cell invasion and migration were detected using transwell and Matrigel experiments, respectively. Bioinformatics and Western blot were applied to investigate the possible underlying mechanism of miR-133b in OSCC.

Results: MiR-133b was lowly expressed in OSCC tissues compared to adjacent normal tissues (p<0.05). Lower expression miR-133b indicated a significantly worse prognosis of OSCC patients (p<0.05). Over-expression of miR-133b reduced the growth and metastasis of SCC9 cells (p<0.05). Transfection of miR-133b inhibitors obviously enhanced the proliferation, migration and invasion of TSC-15 cells (p<0.05). SRY-Box Transcription Factor 4 (SOX4) was verified as a specific target for miR-133b. Up- or down-regulation of miR-133b decreased or increased the protein expression level of SOX4 in OSCC, respectively (p<0.05).

Conclusions: MiR-133b was lowly expressed in OSCC tissues and cell lines. Down-regulation of miR-133b reduced the proliferation, invasion and migration of OSCC cells via regulating SOX4. All our findings suggested that miR-133b could be used as a potential target for the treatment of OSCC.

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / metabolism*

Substances

  • MIRN133 microRNA, human
  • MicroRNAs
  • SOX4 protein, human
  • SOXC Transcription Factors