PTP4A3 is a target for inhibition of cell proliferatin, migration and invasion through Akt/mTOR signaling pathway in glioblastoma under the regulation of miR-137

Abstract

Glioblastoma multiforme (GBM) is one of the most common primary malignant adult brain tumors. It is characterized by aggressive progression and poor prognosis. There is significant need to understand the mechanism of GBM malignancy and develop improved therapeutic options for GBM patients. We systematically studied the function of PTP4A3 in the malignancy of GBM. We found that PTP4A3 was upregulated in GBM tissues and cells. Knockdown of PTP4A3 expression in GBM cells inhibited cell proliferation, migration, and invasion. PTP4A3 knockdown modulated the activity of the Akt/mTOR signaling pathway by inducing de-phosphorylation of Akt and mTOR. We identified PTP4A3 as a direct target of miR-137. MiR-137 has been reported as a tumor suppressor in GBM development. In this study, overexpression of miR-137 in GBM cells also inhibited cell proliferation, migration, and invasion. Finally, restoration of PTP4A3 expression in miR-137 overexpressing cells partially reversed the inhibition of GBM cell malignancy, and the de-phosphorylation of Akt and mTOR. We identified that PTP4A3 regulated GBM via miR-137-mediated Akt/mTOR signaling pathway.