PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

J Orthop Surg Res. 2020 Apr 25;15(1):162. doi: 10.1186/s13018-020-01679-6.

Abstract

Background: This article reports the effects of proenkephalin (PENK) on osteosarcoma (OS) cell migration.

Methods: A Gene Expression Omnibus (GEO) dataset was used to identify differentially expressed genes (DEGs) in OS tumor samples and normal human osteoblasts. Tumor tissue and adjacent normal tissue were collected from 40 OS patients. MG63 cells were transfected with si-PENK. Transwell migration assays and wound healing assays were performed to compare the effect of PENK on migration. Moreover, LY294002 was used to identify the potential mechanism. Gene expression was examined via qRT-PCR and Western blotting.

Results: Bioinformatic analysis revealed that PENK was downregulated in OS tumor samples compared with normal human osteoblasts. Moreover, PENK was identified as the hub gene of the DEGs. The PI3K/Akt signaling pathway was significantly enriched in the DEGs. Moreover, PENK was downregulated in OS and MG63 cells compared with the corresponding control cells. Silencing PENK promoted MG63 cell migration; however, treatment with LY294002 partially attenuated PENK silencing-induced OS cell migration.

Conclusion: PENK inhibits OS cell migration by activating the PI3K/Akt signaling pathway.

Keywords: Akt; Migration; Osteosarcoma; PENK; PI3K.

MeSH terms

  • Adult
  • Blotting, Western
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement* / physiology
  • Enkephalins / metabolism
  • Enkephalins / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Osteoblasts / metabolism
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Precursors / metabolism
  • Protein Precursors / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction*
  • Young Adult

Substances

  • Enkephalins
  • Protein Precursors
  • proenkephalin
  • Proto-Oncogene Proteins c-akt