LncRNA LINC00628 overexpression inhibits the growth and invasion through regulating PI3K/Akt signaling pathway in osteosarcoma

Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5857-5866. doi: 10.26355/eurrev_201809_15915.

Abstract

Objective: Osteosarcoma (OS) is the most common primary malignancy, mainly arising from the metaphysic of the long bones of adolescents and young adults. Although osteosarcoma has been studied widely, the underlying molecular mechanism remains unclear. Increasing evidence shows that abnormal long non-coding RNAs (LncRNAs) expression is involved in tumorigenesis. The aim of this study was to identify the detailed role of LncRNA LINC00628 in osteosarcoma.

Materials and methods: The relative mRNA expression level of LINC00628 in adjacent tissues, osteosarcoma tissues with or without metastasis and osteosarcoma cell lines were detected by qRT-PCR. Overall survival curves for two groups defined by high and low expression level of LINC00628 in osteosarcoma patients. The cell proliferation, invasion and migration in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were detected. The cell cycle distribution and apoptosis rate in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were measured using the Flow cytometry analysis. The relative protein expression level of p-PI3K, p-Akt, P53 and Bcl-2 in osteosarcoma cells after transfection with lncRNA- NC or lncRNA-LINC00628 were detected by Western blot.

Results: LINC00628 expression was significantly decreased in osteosarcoma tissues compared with adjacent tissues. Meanwhile, osteosarcoma tissues with metastasis were significantly associated with a low expression level of LINC00628 and the low expression level of LINC00628 has a lower overall survival rate. LINC00628 expression was increased in osteosarcoma cell lines after transfection with lncRNA-LINC00628 and the cell proliferation, invasion and migration in osteosarcoma cells after transfection with lncRNA-LINC00628 were significantly inhibited. Moreover, the cell cycle was arrested in G0/G1 phase and the apoptosis rate was increased in osteosarcoma cells after transfection with lncRNA-LINC00628. Mechanistically, the relative protein expression level of p-PI3K, p-Akt and Bcl-2 were significantly increased and the relative expression of P53 was significantly decreased in osteosarcoma cells after transfection with lncRNA-LINC00628.

Conclusions: LINC00628 expression was decreased in osteosarcoma. The overexpression of LINC00628 inhibited the proliferation, invasion and migration and promoted cell apoptosis in osteosarcoma cells through the inactivation of PI3K/Akt signaling pathway. This lncRNA may be involved in the development and progression of osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Signal Transduction*
  • Survival Analysis
  • Up-Regulation*

Substances

  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt