miR‑95 promotes osteosarcoma growth by targeting SCNN1A

Oncol Rep. 2020 May;43(5):1429-1436. doi: 10.3892/or.2020.7514. Epub 2020 Feb 24.

Abstract

Osteosarcoma (OS) is a common malignant bone tumor, presenting particularly in children and young adults, and accounts for approximately 19% of all malignant bone cancers. Despite advances in OS treatment, long‑term prognosis remains poor. miRNAs are non‑coding single‑stranded RNAs ~22 nucleotides in length. Increasing evidence suggests that numerous miRNAs may play critical roles in tumorigenesis and tumor progression; however, the role of miR‑95 in OS has not been examined. In the present study, we investigated the role of miR‑95 in OS using in vitro and in vivo models and publicly available expression data. Our findings indicate that abnormal miR‑95 expression occurs in OS, according to the Gene Expression Omnibus (GEO) database. The miR‑95 inhibitor reduced cell proliferation and promoted apoptosis in OS cell lines as detected by EdU staining, TUNEL staining and flow cytometry. Furthermore, a dual luciferase reporter assay revealed that miR‑95 regulates the cell cycle of OS cells and apoptosis by targeting sodium channel epithelial 1α subunit (SCNN1A). Additionally, miR‑95 antagomir suppressed the growth of U2OS xenograft tumors in a mouse model. In summary, our results suggest that miR‑95 induces OS growth in vitro and in vivo by targeting SCNN1A. Our results help clarify the mechanism underlying the miR‑95‑mediated effects on OS tumor growth, thus potentially establishing it as a diagnostic target.

Keywords: osteosarcoma; miR-95; cell cycle; cell apoptosis; SCNN1A.

MeSH terms

  • Animals
  • Apoptosis
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial Sodium Channels / genetics*
  • Epithelial Sodium Channels / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*
  • Prognosis
  • Up-Regulation*

Substances

  • Epithelial Sodium Channels
  • MIRN95 microRNA, human
  • MicroRNAs
  • SCNN1A protein, human