MicroRNA-302a targets GAB2 to suppress cell proliferation, migration and invasion of glioma

Abstract

Glioma is the most frequent and aggressive primary tumor of the brain in humans. Over the last few decades, significant progress has been made in early detection and multi-mode treatments, but the prognosis of gliomas is still extremely poor. MicroRNAs are endogenously expressed non-coding, single strand and short RNA molecules. Increasing number of studies demonstrated that microRNAs are dysregulated in a variety of human cancers, and play significant roles in tumorigenesis and tumor development, including glioma. In the present study, we for the first time found that microRNA-302a (miR- 302a) was significantly downregulated in both glioma tissues and cell lines. In glioma patients, low miR-302a expression was correlated with KPS score and WHO grade. Restoration of miR-302a expression inhibited cell proliferation, migration and invasion of glioma in vitro. In addition, GAB2 was identified as a direct target of miR-320a. In clinical glioma tissues, GAB2 was upregulated and inversely correlated with miR-302a expression. GAB2 underexpression had similar biological roles with miR-302a overexpression in glioma cells, further confirming that GAB2 was a functional downstream target of miR-302a. Moreover, rescue experiments showed that upregulation of GAB2 effectively reversed the inhibition effects of miR-302a on glioma cells proliferation, migration and invasion. These findings suggested that miR-302a is an important tumor suppressor of glioma progression by directly targeting GAB2, thus providing new insight into the molecular mechanisms underlying glioma occurrence, development and evolution of glioma.