机构：[1]Clinical Research and Lab Center, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China[2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China[3]Department of Radiotherapy and Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China[4]Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China[5]Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China[6]The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China[7]North District, The Municipal Hospital of Suzhou, Suzhou, China
We previously identified a pivotal role for G protein alpha inhibitory subunit 1 (G alpha i1) in mediating PI3K-Akt signaling by receptor tyrosine kinases (RTKs). Here, we examined the expression and biological function of G alpha i1 in human glioma. G alpha i1 mRNA and protein expression were significantly upregulated in human glioma tissues, which correlated with downregulation of an anti-G alpha i1 miRNA: microRNA-200a ("miR-200a"). Forced-expression of miR-200a in established (A172/U251MG lines) and primary (patient-derived) human glioma cells resulted in G alpha i1 downregulation, Akt inactivation and proliferation inhibition. Reduction of G alpha i1 expression by shRNA, dominant negative mutant interference, or complete G alpha i1 depletion inhibited Akt activation and cell proliferation. Notably, miR-200a was unable to inhibit glioma cell proliferation when G alpha i1 was silenced or mutated. Co-immunoprecipitation studies, in human glioma cells and tissues, show that G alpha i1 forms a complex with multiple RTKs (EGFR, PDGFR alpha, and FGFR) and the adapter protein Gab1. In vivo, the growth of subcutaneous and orthotopic glioma xenografts in nude mice was largely inhibited by expression of G alpha i1 shRNA or miRNA-200a. Collectively, miR-200a downregulation in human glioma leads to G alpha i1 over-expression, Akt activation and glioma cell proliferation.
基金：
This study was supported in part by grants from
the National Natural Science Foundation of China (81502162,
81771457, 81371055, and 81570859, 81302195, 31371139 and
81502162, 81571282, 81472786, and 81773192); Grants from Natural
Science Foundation of Jiangsu Province (BK20130301, BK20170060,
and BK20171248), and by Clinical Special Project of Suzhou
(LCZX201601)
第一作者机构：[1]Clinical Research and Lab Center, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China[2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China[5]Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China[6]The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China[7]North District, The Municipal Hospital of Suzhou, Suzhou, China
推荐引用方式(GB/T 7714)：
Yuan-yuan Liu,Min-Bin Chen,Long Cheng,et al.microRNA-200a downregulation in human glioma leads to G alpha i1 over-expression, Akt activation, and cell proliferation[J].ONCOGENE.2018,37(21):2890-2902.doi:10.1038/s41388-018-0184-5.
APA：
Yuan-yuan Liu,Min-Bin Chen,Long Cheng,Zhi-qing Zhang,Zheng-quan Yu...&Cong Cao.(2018).microRNA-200a downregulation in human glioma leads to G alpha i1 over-expression, Akt activation, and cell proliferation.ONCOGENE,37,(21)
MLA：
Yuan-yuan Liu,et al."microRNA-200a downregulation in human glioma leads to G alpha i1 over-expression, Akt activation, and cell proliferation".ONCOGENE 37..21(2018):2890-2902
医学