GNAI1 Suppresses Tumor Cell Migration and Invasion and is Post-Transcriptionally Regulated by Mir-320a/c/d in Hepatocellular Carcinoma

Objective To explore the role and regulation of guanine nucleotide-binding protein G(i),α-1 subunit(GNAI1) in hepatocellular carcinoma(HCC). Methods 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. Results 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. Conclusions 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.

Role of micro RNAs in inflammation-associated liver cancer

Liver cancer, primarily hepatocellular carcinoma(HCC), is a major cause of cancer-related death worldwide. HCC is a suitable model of inflammation-induced cancer because more than 90% of HCC cases are caused by liver damage and chronic inflammation. Several inflammatory response pathways, such as NF-κB and JAK/STAT3 signaling pathways, play roles in the crosstalk between inflammation and HCC. MicroRNAs(miRNAs) are evolutionarily conserved, short endogenous, non-coding single-stranded RNAs that are involved in various biological and pathological processes by regulating gene expression and protein translation. Evidence showed that miRNAs play a pivotal role in hepatitis virus infection and serve as promoters or inhibitors of inflammatory response. Aberrant miRNA was observed during liver inflammation and HCC. Many dysregulated miRNAs modulate the initiation and progression of inflammation-induced HCC. This review summarizes the role and functions of miRNAs in inflammation-associated HCC, as well as the designed therapeutics targeting miRNAs to treat liver inflammation and HCC.