MicroRNA-29a-3p Downregulation Causes Gab1 Upregulation to Promote Glioma Cell Proliferation.

ABSTRACT

BACKGROUND/AIMS: Glioma causes significant human mortalities annually. Molecularly-targeted therapy is a focus of glioma research. METHODS: Grb2-associated binding 1 (Gab1) expression and microRNA-29a-3p ("miR-29a-3p") expression in human glioma cells and tissues were tested by Western blotting assay and qRT-PCR assay. shRNA/siRNA strategy was applied to silence Gab1 in human glioma cells. miR-29a or anti-sense miR-29a construct was transfected to human glioma cells. Cell proliferation was tested by BrdU ELISA assay and cell counting assay. RESULTS: We show that expression of Gab1 was significantly elevated in human glioma tissues and cells, which correlated with downregulation of its putative microRNA miR-29a-3p. In A172 glioma cells and primary human glioma cells, Gab1 shRNA/siRNA inhibited Akt-Erk activation and cell proliferation. Forced-expression of miR-29a-3p downregulated Gab1, inhibiting glioma cell proliferation, whereas miR-29a-3p was in-effective on cell proliferation in Gab1-silenced A172 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant Gab1 (UTR-G160A) blocked miR-29a-3p-induced inhibition on Akt signaling and A172 cell proliferation. CONCLUSIONS: miR-29a-3p downregulation leads to Gab1 upregulation to promote glioma cell proliferation.