GNAI1 Suppresses Tumor Cell Migration and Invasion and is Post-Transcriptionally Regulated by Mir-320a/c/d in Hepatocellular Carcinoma
Open Access
- 1 December 2012
- journal article
- Vol. 9 (4), 234-241
- https://doi.org/10.7497/j.issn.2095-3941.2012.04.003
Abstract
To explore the role and regulation of guanine nucleotide-binding protein G(i), α-1 subunit (GNAI1) in hepatocellular carcinoma (HCC). Expression of GNAI1 in HCC samples was determined by qRT–PCR and immunohistochemical (IHC) staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAI1 was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. GNAI1 is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.Keywords
This publication has 28 references indexed in Scilit:
- Inhibitory heterotrimeric GTP-binding proteins inhibit hydrogen peroxide-induced apoptosis by up-regulation of Bcl-2 via NF-κB in H1299 human lung cancer cellsBiochemical and Biophysical Research Communications, 2009
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009
- Differential partitioning of Gαi1 with the cellular microtubules: a possible mechanism of development of Taxol resistance in human ovarian carcinoma cellsJournal of Molecular Signaling, 2006
- The Hippo Pathway Regulates the bantam microRNA to Control Cell Proliferation and Apoptosis in DrosophilaCell, 2006
- Reciprocal Signaling between the Transcriptional Co-Factor Eya2 and Specific Members of the Gαi FamilyMolecular Pharmacology, 2004
- G protein coupled receptor signaling through the Src and Stat3 pathway: role in proliferation and transformationOncogene, 2001
- G protein G?q/11 and G?i1,2 are activated by pancreastatin receptors in rat liver: Studies with GTP-?35S and azido-GTP-?-32PJournal of Cellular Biochemistry, 1999
- Inhibition of Adenylyl Cyclase by G iαScience, 1993
- Diversity of G Proteins in Signal TransductionScience, 1991
- G PROTEINS: TRANSDUCERS OF RECEPTOR-GENERATED SIGNALSAnnual Review of Biochemistry, 1987