title: GNAI3 inhibits tumor cell migration and invasion and is post-transcriptionally regulated by miR-222 in hepatocellular carcinoma.
abstract: Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (GNAI3) is involved in many biological processes. However, its biological function in hepatocellular carcinoma (HCC) remains unclear. An immunohistochemical staining analysis revealed that GNAI3 protein was down-regulated in HCC compared to non-cancerous liver. Furthermore, transwell assays indicated that GNAI3 inhibits HCC cell migration and invasion. Using software predictions and experimental screening, we found that miR-222 could directly bind to GNAI3 mRNA and decrease GNAI3 protein expression in HCC cells. Moreover, miR-222 was up-regulated in HCC and negatively correlated with GNAI3 protein expression. These results indicated that down-regulation of GNAI3 might be caused by up-regulation of miR-222 in HCC. In conclusion, GNAI3 was down-regulated by miR-222 in HCC, and this deregulation promoted migration and invasion of HCC. These findings extended our insight into the complex molecular mechanisms underlying the invasion and metastasis of HCC and may provide new therapeutic targets.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment for Infectious Diseases, The first Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huan
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Lian
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Chuanyang
authors.initials: C
authors.lastname: Bao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: lianglinhui@fudan.edu.cn.
authors.forename: Linhui
authors.initials: L
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China; Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: xhhe@shsci.org.
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D035683:MicroRNAs; D012333:RNA, Messenger; C525710:MIR222, human; C498819:GNAI3 protein, human
keywords: GNAI3; Hepatocellular carcinoma; Invasion; Migration; miR-222