miR-423-5p Inhibits Osteosarcoma Proliferation and Invasion Through Directly Targeting STMN1

Cell Physiol Biochem. 2018;50(6):2249-2259. doi: 10.1159/000495085. Epub 2018 Nov 13.

Abstract

Background/aims: Increasing evidences suggest that dysregulated expression of miRNAs contributes to the progression of various tumors. However, the underlying function of miR-423-5p in osteosarcoma remains unexplored.

Methods: The expression of miR-423-5p and STMN1 were determined in osteosarcoma samples and cell lines via quantitative real-time PCR. Colony formation and Cell Counting Kit-8 (CCK-8) assays were performed to measure cell proliferation ability and transwell analysis was used to detect cell invasion, and dual luciferase reporter assay was perform to analysis the interaction between the miR-423-5p and STMN1.

Results: The expression levels of miR-423-5p and STMN1 in the osteosarcoma tissues and cell lines were measured by qRT-PCR. Cell viability was determined using the clone formation and CCK-8 assays. A dual-luciferase reporter and Western blot were performed to stdudy the target gene of miR-423-5p. Here, we showed that miR-423-5p expression was downregulated in osteosarcoma tissues and cell lines. However, the expression of stathmin1 (STMN1) was downregulated in osteosarcoma tissues and cell lines. Moreover, STMN1 expression level was negatively correlated with the miR-423-5p expression in the osteosarcoma tissues. We identified STMN1 was a direct target gene of miR-423-5p in osteosarcoma cell. Overexpression of miR-423-5p inhibited osteosarcoma cell proliferation, colony formation and invasion. Furthermore, we demonstrated that STMN1 was involved in miR-423-5p-mediated cell behavior such as cell proliferation, colony formation and invasion in the osteosarcoma cell.

Conclusion: Our present study indicated that miR-423-5p acted as a tumor suppressor gene in osteosarcoma partly through inhibiting STMN1 expression.

Keywords: MicroRNAs; Osteosarcoma; STMN1; miR-423-5p.

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / metabolism
  • Base Sequence
  • Binding Sites
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutagenesis
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Sequence Alignment
  • Stathmin / chemistry
  • Stathmin / genetics
  • Stathmin / metabolism*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MIRN423 microRNA, human
  • MicroRNAs
  • STMN1 protein, human
  • Stathmin