MicroRNA-126 acts as a tumor suppressor in glioma cells by targeting insulin receptor substrate 1 (IRS-1)

MicroRNA (miR-126) was reported to be downregulated and to act as a tumor suppressor in cancers of the lung, cervix, bladder, breast, liver and prostate. However, the precise roles and underling mechanisms of miR-126 in glioma remain largely unknown. This study is aimed to study the role of miR-126 in the progression of glioma and to elucidate underlying miR-126-mediated mechanisms in glioma. Our results revealed that miR-126 was downregulated in the collected glioma specimen, compared with non-cancerous brain tissues. Restored miR-126 expression inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest at G0/G1 phase and cell apoptosis of U-87 MG glioma cells. Overexpression of miR-126 was also able to suppress the growth of U-87 MG glioma xenografts in mice. Furthermore, insulin receptor substrate 1 (IRS-1) were identified as a target of miR-126, and showed that it was negatively regulated by miR-126 in glioma cells. We also demonstrated that overexpression of miR-126 suppressed PI3K and AKT activation, which contribute to suppress tumor growth of glioma. Taken together, these findings showed that miR-126 functions as a tumor suppressor in glioma cells by targeting IRS-1 expression via the PI3K/AKT signaling pathways, suggesting that miR-126 might be a novel target for therapeutic strategies in glioma.