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

MicroRNA-29a-3p Downregulation Causes Gab1 Upregulation to Promote Glioma Cell Proliferation
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MicroRNA-29a-3p 下调导致 Gab1 上调,促进胶质瘤细胞增殖

DOI:
10.1159/000491776
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发表时间:
2018-01-01
影响因子:
--
通讯作者:
Cao, Cong
Cao, Cong
中科院分区:
医学1区
文献类型:
--
作者:
Shao, Nai-yuan;Wang, Dong-xing;Cao, Cong

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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