Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 May;37(21):2890-2902.
doi: 10.1038/s41388-018-0184-5. Epub 2018 Mar 9.

microRNA-200a downregulation in human glioma leads to Gαi1 over-expression, Akt activation, and cell proliferation

Affiliations

microRNA-200a downregulation in human glioma leads to Gαi1 over-expression, Akt activation, and cell proliferation

Yuan-Yuan Liu et al. Oncogene. 2018 May.

Abstract

We previously identified a pivotal role for G protein α inhibitory subunit 1 (Gαi1) in mediating PI3K-Akt signaling by receptor tyrosine kinases (RTKs). Here, we examined the expression and biological function of Gαi1 in human glioma. Gαi1 mRNA and protein expression were significantly upregulated in human glioma tissues, which correlated with downregulation of an anti-Gαi1 miRNA: microRNA-200a ("miR-200a"). Forced-expression of miR-200a in established (A172/U251MG lines) and primary (patient-derived) human glioma cells resulted in Gαi1 downregulation, Akt inactivation and proliferation inhibition. Reduction of Gαi1 expression by shRNA, dominant negative mutant interference, or complete Gαi1 depletion inhibited Akt activation and cell proliferation. Notably, miR-200a was unable to inhibit glioma cell proliferation when Gαi1 was silenced or mutated. Co-immunoprecipitation studies, in human glioma cells and tissues, show that Gαi1 forms a complex with multiple RTKs (EGFR, PDGFRα, 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 Gαi1 shRNA or miRNA-200a. Collectively, miR-200a downregulation in human glioma leads to Gαi1 over-expression, Akt activation and glioma cell proliferation.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Nat Rev Neurosci. 2011 Aug 03;12(9):495-508 - PubMed
    1. Oncotarget. 2016 Oct 25;7(43):70613-70622 - PubMed
    1. Cancer Lett. 2013 May 1;331(2):139-46 - PubMed
    1. Biosci Rep. 2015 Sep 04;35(5):null - PubMed
    1. Oncotarget. 2016 Sep 13;7(37):60123-60132 - PubMed

Publication types

Substances

LinkOut - more resources