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 invitro. In addition, GAB2 was identified as a direct target of miR-320a. In clinical glioma tissues, GAB2 was upregulated and in-versely correlated with miR-302a expression. GAB2 underexpression had similar biological roles with miR-302a overexpression in glio-ma 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.
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