Upregulation of miRNA-154-5p prevents the tumorigenesis of osteosarcoma

Biomed Pharmacother. 2020 Apr:124:109884. doi: 10.1016/j.biopha.2020.109884. Epub 2020 Jan 27.

Abstract

Background: Osteosarcoma (OS) is a primary malignant bone sarcoma in human worldwide. It has been shown that the level of microRNA-154-5p (miR-154-5p) was downregulated in human OS tissues. However, the mechanisms by which miR-154-5p regulates the proliferation, apoptosis and invasion in OS remain unclear. Thus, the present study aimed to investigate the role of miR-154-5p during the tumorigenesis of OS.

Methods: The level of miR-154-5p in human OS tissues was detected by RT-qPCR. In addition, the effects of miR-154-5p on apoptosis and invasion of OS cells were assessed by flow cytometry and transwell assays, respectively. Meanwhile, the dual luciferase reporter system assay was performed to explore the interaction of miR-154-5p and E2F5.

Results: The level of miR-154-5p was downregulated in OS tissues. Overexpression of miR-154-5p significantly inhibited the proliferation, migration and invasion of MG63 cells. In addition, upregulation of miR-154-5p obviously induced apoptosis in MG63 cells via upregulation of Bax and cleaved caspase 3, and downregulation of Bcl-2. Moreover, luciferase reporter assay identified that E2F5 was the binding target of miR-154-5p. Meanwhile, overexpression of miR-154-5p induced cell cycle arrest in MG63 cells via inhibiting the expressions of E2F5, Cyclin E1 and CDK2. Furthermore, in vivo assays indicated that overexpression of miR-154-5p notably inhibited the tumor growth in an OS xenograft model.

Conclusion: These results indicated that miR-154-5p may function as a potential tumor suppressor in OS. Therefore, miR-154-5p might be a novel therapeutic option for the treatment of OS.

Keywords: E2F5; Osteosarcoma; Tumorigenesis; microRNA-154-5p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • MIRN154 microRNA, human
  • MicroRNAs