miR‑144 suppresses proliferation and induces apoptosis of osteosarcoma cells via direct regulation of mTOR expression

Abstract

Studied as a type of tumor suppressor, microRNA (miR) performs an important role in growth and apoptosis of various human carcinomas. However, the effects of miR-l44 on osteosarcoma growth and apoptosis, as well as possible underlying mechanisms, remain unclear. The present study investigated the expression of miR-144 in osteosarcoma MG-63 and U-2 OS cell lines compared with osteoblast cells. In order to elucidate the effects of miR-144 on osteosarcoma, miR-144 was upregulated in MG-63 and U-2 OS cells by transfecting chemically synthesized miR-144 mimics. Bioinformatics analysis of potential miR-144 target genes was performed using TargetScanHuman 7.0 and confirmed by luciferase assay. This analysis identified mammalian target of rapamycin (mTOR) as a target of miR-144. The present results indicated that the overexpression of miR-144 may significantly inhibit proliferation and promote apoptosis of MG-63 and U-2 cells compared with scramble control. Furthermore, the effects of miR-144 on osteosarcoma were associated with the mTOR signaling pathway via directly targeting the 3' untranslated region of mTOR mRNA, resulting in a decrease in the level of mTOR protein. In summary, miR-144 was demonstrated to act as a tumor suppressor, which inhibits proliferation and promotes apoptosis of osteosarcoma cell lines. In addition, this effect was mediated by direct targeting on mTOR following inhibition of the mTOR signaling pathway. The present study suggested that miR-144 may be a candidate for the gene therapy of osteosarcoma.