High expression of G-protein signaling modulator 2 in hepatocellular carcinoma facilitates tumor growth and metastasis by activating the PI3K/AKT signaling pathway

• Published in: Tumor biology 2017-03, Vol.39 (3), p.1010428317695971-1010428317695971
• Main Authors: He, Xiao-Qin, Zhang, Yue-Feng, Yu, Jia-Jun, Gan, Yuan-Yuan, Han, Na-Na, Zhang, Mei-Xia, Ge, Wei, Deng, Jun-Jian, Zheng, Yong-Fa, Xu, Xi-Ming
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adult; Aged; AKT protein; Apoptosis; Apoptosis - genetics; Authorship; Bax protein; Cancer therapies; Carcinogenesis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Caspase; Caspase-3; Cell cycle; Cell Cycle - genetics; Cell division; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Cyclin-dependent kinase; Cyclin-dependent kinase 4; Cyclin-dependent kinase 6; Data processing; E-cadherin; Experiments; Female; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Hepatitis; Hepatitis B; Hepatocellular carcinoma; Humans; Intracellular Signaling Peptides and Proteins - biosynthesis; Intracellular Signaling Peptides and Proteins - genetics; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Metalloproteinase; Metastases; Metastasis; Middle Aged; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Metastasis; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Patients; Phosphatidylinositol 3-Kinase - genetics; Polymerase chain reaction; Proteins; Proto-Oncogene Proteins c-akt - genetics; Signal Transduction; Statistical analysis; Surgery; Therapeutic applications; Tumor cell lines; Vimentin; Western blotting
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1177/1010428317695971

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.