LncRNA GAS5 Suppresses the Proliferation and Invasion of Osteosarcoma Cells via the miR-23a-3p/PTEN/PI3K/AKT Pathway

• Published in: Cell transplantation Vol. 29; p. 96368972095309
• Main Authors: Liu, Jianmin, Chen, Ming, Ma, Longyang, Dang, Xingbo, Du, Gongliang
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2020; Sage Publications Ltd; SAGE Publishing
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Bone cancer; Cell growth; Cell proliferation; Immunoprecipitation; Kinases; Metastases; Original; Osteosarcoma; Osteosarcoma cells; PTEN protein; Reporter gene; Ribonucleic acid; RNA; Sarcoma; Tensin; Tumor suppressor genes; Xenografts; long noncoding RNA; phosphatase and tensin homolog; miR-23a-3p; growth arrest special 5; osteosarcoma
• ISSN: 0963-6897; 1555-3892; 1555-3892
• DOI: 10.1177/0963689720953093

Accumulating evidence has shown that long noncoding RNA GAS5 is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is still largely unclear. In this study, we found that GAS5 was downregulated in human osteosarcoma tissues and cell lines compared with matched adjacent tissues and normal osteoblast cells. Overexpression of GAS5 could significantly suppress the growth and invasion of osteosarcoma cells, while downregulation of GAS5 promoted cell proliferation and invasion. We confirmed that GAS5 could directly bind with miR-23a-3p by using luciferase reporter gene and RNA immunoprecipitation and pull-down assay. Downregulation of miR-23a-3p repressed cell proliferation and invasion. Overexpression of miR-23a-3p counterbalanced the inhibition effect of GAS5 on cell proliferation and invasion. Further studies indicated that overexpression of GAS5 inhibited cell proliferation and metastasis by regulating phosphatase and tensin homolog (PTEN). PTEN was authenticated as a target of miR-23a-3p. Upregulation of GAS5 or silence of miR-23a-3p increased the level of PTEN, while downregulation of GAS5 or overexpression of miR-23a-3p suppressed the expression of PTEN. In addition, overexpression of GAS5 could neutralize the effect of downregulating PTEN on osteosarcoma cell functions. We proved that GAS5 regulated the viability and invasion of osteosarcoma cells through the PI3K/AKT pathway. Moreover, overexpression of GAS5 could inhibit tumor growth in a xenograft nude mouse model in vivo. In summary, GAS5 functions as a competing endogenous RNA, sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.