miR-376a inhibits the proliferation and invasion of osteosarcoma by targeting FBXO11

Hum Cell. 2019 Jul;32(3):390-396. doi: 10.1007/s13577-019-00256-2. Epub 2019 May 11.

Abstract

Dysregulation of microRNAs (miRNAs) is frequently found in the tumorigenesis of osteosarcoma (OS). miR-376a was found to play tumor suppressive roles in human cancers. However, the role of miR-376a in OS remains unclear. The expression of miR-376a was analyzed by quantitative real-time PCR (qRT-PCR) in OS cell lines. Cell proliferation assay, cell invasion assay, and cell apoptosis assay were performed to detect the biological function of miR-376a after synthetic miRNA transfection. The target of miR-376a was predicted by TargetScan and miRDB, and further validated by luciferase activity reporter assay and western blot. miR-376a expression was revealed to be decreased in OS cell lines. In vitro experiments showed that overexpression of miR-376a inhibits OS cell proliferation and invasion but promotes apoptosis. Luciferase activity reporter assay and western blot assay showed F-box protein 11 (FBXO11) was a direct target of miR-376a. Furthermore, FBXO11 mediated the role of miR-376a on the proliferation, invasion, and apoptosis of OS cells. Collectively, these results revealed miR-376a functions as a tumor suppressor by targeting FBXO11 in OS. It may be developed as a therapeutic target for OS patients.

Keywords: FBXO11; Osteosarcoma; Tumor suppressive miRNA; miR-376a.

Publication types

  • Retracted Publication

MeSH terms

  • Apoptosis / genetics
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism*
  • Gene Expression*
  • Genes, Tumor Suppressor*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • MicroRNAs / physiology
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • Osteosarcoma / therapy
  • Protein-Arginine N-Methyltransferases / genetics*
  • Protein-Arginine N-Methyltransferases / metabolism*

Substances

  • F-Box Proteins
  • MIRN376C microRNA, human
  • MicroRNAs
  • FBXO11 protein, human
  • Protein-Arginine N-Methyltransferases