机构：[a]Department of Neurosurgery, the Third Affiliated Hospital of Soochow University, Changzhou,[b]Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou,[c]Institute of Neuroscience, Soochow University, Suzhou,[d]The Affiliated Eye Hospital, Nanjing Medical University, Nanjing,[e]North District, The Municipal Hospital of Suzhou, Suzhou, China
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: miR29a-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. (C) 2018 The Author(s) Published by S. Karger AG, Basel
基金：
This work was generously supported by grants from the National Natural Science Foundation of China (Nos. 81371055 and 81570859, 81302195, 31371139 and 81502162, 81571282); Grants from Natural Science Foundation of Jiangsu Province (BK20130301, BK20151213, BK20170060), and Jiangsu province Six-Talent Peaks (To C.C.).
