MiR-524 suppressed the progression of oral squamous cell carcinoma by suppressing Metadherin and NF-κB signaling pathway in OSCC cell lines

Arch Oral Biol. 2021 May:125:105090. doi: 10.1016/j.archoralbio.2021.105090. Epub 2021 Feb 22.

Abstract

Objectives: The aim of the present study was to explore the functional role of miR-524 in oral squamous cell carcinoma (OSCC) and determine its underlying mechanism.

Materials and methods: Tumor tissues and adjacent tissues were obtained from 55 patients with OSCC (20 females and 35 males) with a mean age of 54 years (range from 24 to 72 years). Additionally, OSCC cell lines culture was used and Reverse transcription‑quantitative PCR (RT-qPCR) was applied to measure the expression of miR-524 in OSCC tissues and cells. The protein density of Metadherin (MTDH) in OSCC tissues was detected by Immunohistochemistry (IHC) assay. MiR-524 mimic was employed to investigate the impact of miR-524 on proliferation, migration, and invasion using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and transwell assays. The dual luciferase reporter assay was utilized to investigate the interaction between MTDH and miR-524 expression. Cells transfected with miR-524 mimic and pcDNA-MTDH were subjected to western blot to investigate the role of NF-κB signaling in miR-524/MTDH axis mediated cell proliferation, migration, and invasion.

Results: MiR-524 expression was decreased significantly in OSCC tissues compared to adjacent tissues, and closely related to clinical stage, tumor size, and lymph node metastasis. Over-expression of miR-524 suppressed the proliferation, migration, and invasion of OSCC cells. Luciferase reporter assay results demonstrated that MTDH was the target gene of miR-524. Over-expression of miR-524 reduced MTDH expression and inhibited NF-κB signaling pathway. Rescue experiments revealed that over-expression of MTDH partially reversed the efficacy of miR-524 mimic on OSCC cells.

Conclusions: These results indicated that miR-524 inhibits the activation of NF-κB signaling pathway via inhibiting MTDH, resulting in the suppression of cell proliferation, migration, and invasion.

Keywords: MTDH; NF-κB; OSCC; miR-524.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms*
  • Humans
  • Male
  • Membrane Proteins
  • MicroRNAs* / genetics
  • Middle Aged
  • Mouth Neoplasms* / genetics
  • NF-kappa B
  • RNA-Binding Proteins
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck
  • Young Adult

Substances

  • MIRN-524 microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • NF-kappa B
  • RNA-Binding Proteins