Up-regulation of LINC00619 promotes apoptosis and inhibits proliferation, migration and invasion while promoting apoptosis of osteosarcoma cells through inactivation of the HGF-mediated PI3K-Akt signalling pathway

Epigenetics. 2022 Jan-Feb;17(2):147-160. doi: 10.1080/15592294.2021.1890873. Epub 2021 Apr 2.

Abstract

This study is performed to evaluate the role of long noncoding RNA (lncRNA) LINC00619 in osteosarcoma through the PI3K-Akt signalling pathway by binding to HGF. Osteosarcoma and osteochondroma tissues from patients were collected. The relationship between lncRNA LINC00619 and HGF was proved by the dual-luciferase reporter gene assay. The expression patterns of lncRNA LINC00619 as well as the levels of proliferating cell nuclear antigen (PCNA), hepatocyte growth factor (HGF), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), Bax, Bcl-2, alkaline phosphatase (ALP), and osteopontin (OPN) were detected by RT-qPCR and Western blot analysis. In addition, MTT assay, flow cytometry, scratch test, and Transwell assay were performed to assess the cell proliferation, cell cycle distribution, apoptosis, cell migration, and invasion in each group, respectively. Osteosarcoma tissues presented with elevated positive expression rate of HGF, up-regulated expression levels of PCNA, HGF, PI3K, Akt, Bcl-2, ALP and OPN, and down-regulated expressions of Bax and LINC00619. HGF was verified as a target gene of lncRNA LINC00619. LINC00619 was found to down-regulate the expressions of PCNA, HGF, PI3K, Akt, Bcl-2, ALP, and OPN in osteosarcoma cells. Up-regulation of lncRNA LINC00619 decreased cell growth, migration intensity, and invasion ability, but enhanced the apoptosis rate of osteosarcoma cells. Our findings suggest that lncRNA LINC00619 inhibits proliferation, migration and invasion and improves apoptosis of osteosarcoma cells through the inhibition of the activation of the HGF-dependent PI3K-Akt signalling pathway.

Keywords: HGF; Long noncoding RNA LINC00619; PI3K-Akt signalling pathway; apoptosis; osteosarcoma; proliferation.

MeSH terms

  • Apoptosis / genetics
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Up-Regulation

Substances

  • HGF protein, human
  • RNA, Long Noncoding
  • Hepatocyte Growth Factor
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt