TRPM2-AS promotes the malignancy of osteosarcoma cells by targeting miR-15b-5p/PPM1D axis

Cell Cycle. 2022 Apr;21(8):835-850. doi: 10.1080/15384101.2022.2033414. Epub 2022 Jan 31.

Abstract

Osteosarcoma (OS) is a malignant tumor with a low survival rate and a high incidence rate worldwide. Although research has reported the involvement of long non-coding RNAs (lncRNAs) in the pathogenesis of OS cells, the role of TRPM2-AS, miR-15b-5p, and PPM1D in OS progression remains unclear. This study aimed to examine the interaction of the TRPM2-AS/miR-15b-5p/PPM1D axis in OS cells to gain new insights into the molecular mechanism and pathogenesis of OS. After performing in vitro functional assays, we discovered that TRPM2-AS was overexpressed in OS cells. TRPM2-AS silencing impaired OS cell viability, proliferation, and migration, while it induced apoptosis in OS cells in vitro. Our experimental analysis also revealed that PPM1D is a direct target of miR-15b-5p. TRPM2-AS silencing was found to reverse the tumorigenic effect of the miR-15b-5p inhibitor, while the miR-15b-5p inhibitor restored the inhibition of OS caused by silencing PPM1D. Moreover, our findings revealed that miR-15b-5p exerted its tumor-suppressive role by directly targeting PPM1D. In conclusion, this study suggests that TRPM2-AS could promote OS cell malignancy by sponging miR-15b-5p/PPM1D axis.

Keywords: PPM1D; TRPM2-AS; miR-15b-5p; osteosarcoma.

MeSH terms

  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Osteosarcoma* / genetics
  • Osteosarcoma* / pathology
  • Protein Phosphatase 2C
  • TRPM Cation Channels* / genetics

Substances

  • MicroRNAs
  • TRPM Cation Channels
  • TRPM2 protein, human
  • PPM1D protein, human
  • Protein Phosphatase 2C

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.