MiR-139 inhibits proliferation, migration and invasion of osteosarcoma cell line MG63 via down-regulating integrin subunit alpha V(ITGAV)

Abstract

Objectives: Osteosarcoma is a relatively common primary malignant bone tumor in clinic, which frequently occurs in children and adolescents. It is essential to clarify the molecular mechanism of osteosarcoma to provide better diagnosis and treatment. Abnormal expression of miRNAs is closely related to the pathogenesis and progression of osteosarcoma. MiRNAs play a regulatory role in tumorigenesis and development of osteosarcoma. The purpose of this study is to reveal the working mechanism of miR-139/ITGAV axis in osteosarcoma progression.

Methods: ITGAV and miR-139 expression was detected in osteosarcoma tissues or paracancerous normal tissues. TargetScan and Double luciferase reporter gene assay were adopted to verify weather ITGAV was the target gene of miR-139. Western blot and qRT-PCR were used to evaluate the effects of miR-139 on ITGAV. CCK8, Flow cytometry, Transwell and Cell wound scratch assay were used to measure the effects of miR-139 and ITGAV on cell cycle, proliferation, migration and invasion of MG63, respectively. A nude mouse xenograft model of cervical cancer was constructed to observe the effects of miR-139 on the tumor growth.

Results: We found that the expression of miR-139 in osteosarcoma tissue was significantly reduced, while the expression of ITGAV was significantly increased. MiR-139 could specifically bind to the 3'-UTR of ITGAV and negatively regulate its expression. Transfection of miR-139 mimic could inhibit the proliferation, S-phase arrest, invasion and migration of MG63 cells, and up-regulating the expression of ITGAV could reverse such inhibitory effect. In nude mouse xenograft model of osteosarcoma, overexpression of miR-139 could inhibit tumor growth, while down-regulation of miR-139 produced the opposite effect.

Conclusions: These results indicate that miR-139/ITGAV axis was related to osteosarcoma initiation. MiR-139 could inhibit the biological behavior of osteosarcoma cells and the tumor growth in nude mouse model via targeting ITGAV, and miR-139/ITGAV axis may impede the progression of osteosarcoma.

Keywords: ITGAV; miR-139; osteosarcoma.