title: High expression of G-protein signaling modulator 2 in hepatocellular carcinoma facilitates tumor growth and metastasis by activating the PI3K/AKT signaling pathway.
abstract: The aim of this study was to investigate the role of G-protein signaling modulator 2 in the carcinogenesis and progression of hepatocellular carcinoma. We previously showed that G-protein signaling modulator 2 was upregulated in hepatitis B virus-related hepatocellular carcinoma tissues through a hierarchical clustering analysis. With this study, we first assessed the expression pattern of G-protein signaling modulator 2 in hepatocellular carcinoma specimens and adjacent noncancerous tissues; clinical data were analyzed, along survival times, utilizing the Kaplan-Meier method. Moreover, the functions of G-protein signaling modulator 2 were examined using small-interfering RNAs in vitro. The results showed that G-protein signaling modulator 2 was clearly overexpressed in hepatocellular carcinoma tissues and cell lines and that the G-protein signaling modulator 2 expression level was related to tumor size and hepatitis B virus infection. Furthermore, G-protein signaling modulator 2 knockdown studies suggested that G-protein signaling modulator 2 accelerates cell growth, cell cycle, migration, and invasion and inhibits apoptosis, acting as an oncogene in hepatocellular carcinoma. Western blotting indicated that silencing of G-protein signaling modulator 2 in HepG2 and SMMC-7721 cells increased the expression levels of Bax, caspase-3, and E-cadherin, while notably suppressing the cyclin-dependent kinase 4, cyclin-dependent kinase 6, CyclinD1, Snail1, Vimentin, and matrix metallopeptidase 9 expression levels, compared with that in the control groups. In addition, we found that G-protein signaling modulator 2 can affect the expression of key proteins involved in protein kinase B activation. In conclusion, high expression of G-protein signaling modulator 2 was involved in the pathological processes of hepatocellular carcinoma through activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which may provide an attractive potential diagnostic biomarker and therapeutic target for treatment of hepatocellular carcinoma.
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: He
authors.affiliation: 2 Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Gan
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Han
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Mei-Xia
authors.initials: MX
authors.lastname: Zhang
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Deng
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Yong-Fa
authors.initials: YF
authors.lastname: Zheng
authors.affiliation: 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction
chemical_list: C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: G-protein coupled receptor; G-protein signaling modulator 2; metastasis; phosphatidylinositol 3-kinase/protein kinase B; proliferation