MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma

Weixin Xie1, Jie Xiao2, Tao Wang3

  • 1Department of Orthopaedic Surgery, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.

Insights

MicroRNA-876-5p (miR-876-5p) is down-regulated in osteosarcoma (OS), suppressing tumor growth and progression. Low miR-876-5p levels correlate with poor prognosis, suggesting its potential as a diagnostic and therapeutic target for OS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Aberrant microRNA (miRNA) expression is implicated in human cancer progression.
  • The role of miR-876-5p in osteosarcoma (OS) remains uncharacterized.

Purpose of the Study:

  • To investigate the expression, function, and clinical significance of miR-876-5p in osteosarcoma.
  • To elucidate the underlying molecular mechanisms of miR-876-5p in OS progression.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) for miR-876-5p expression analysis in OS tissues and cell lines.
  • Gain- and loss-of-function assays (transfection with miR-876-5p mimics and inhibitors) to assess cellular proliferation, migration, and invasion.
  • In vivo tumor xenograft models in mice to evaluate the effect of miR-876-5p overexpression on tumor growth.
  • Luciferase reporter assays to confirm c-Met as a direct target of miR-876-5p.

Main Results:

  • miR-876-5p expression was significantly downregulated in OS tissues compared to adjacent normal tissues.
  • Downregulation of miR-876-5p correlated with advanced clinical stage, poor differentiation, and shorter overall survival in OS patients.
  • Restoration of miR-876-5p suppressed OS cell proliferation, migration, and invasion, while knockdown promoted these processes.
  • Overexpression of miR-876-5p inhibited OS tumor growth in vivo.
  • miR-876-5p directly targeted c-Met, reducing its expression in OS cells and tissues.
  • Restoration of c-Met expression rescued the inhibitory effects of miR-876-5p on OS cell behaviors.

Conclusions:

  • miR-876-5p functions as a tumor suppressor in osteosarcoma.
  • miR-876-5p inhibits OS cell proliferation, migration, and invasion by targeting c-Met.
  • miR-876-5p may serve as a potential therapeutic target and prognostic biomarker for osteosarcoma.

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