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

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.

Download Full-text

Hepatocellular carcinoma progression mediated by hepatitis B virus-encoded circRNA HBV_circ_1 through interaction with cyclin-dependent kinase 1

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2021.08.011 ◽

2021 ◽

Author(s):

Min Zhu ◽

Zi Liang ◽

Jun Pan ◽

Xing Zhang ◽

Renyu Xue ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Cyclin Dependent Kinase ◽

B Virus

Download Full-text

Reduction of double-stranded RNA-activated protein kinase in hepatocellular carcinoma associated with hepatitis B virus

Journal of Medical Virology ◽

10.1002/jmv.20074 ◽

2004 ◽

Vol 73 (2) ◽

pp. 187-194 ◽

Cited By ~ 7

Author(s):

George G. Chen ◽

Paul B.S. Lai ◽

Rocky L.K. Ho ◽

Paul K.S. Chan ◽

H. Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Protein Kinase ◽

Hepatitis B ◽

Double Stranded Rna ◽

B Virus

Download Full-text

Raf-1 and protein kinase B regulate cell survival through the activation of NF-κB in hepatitis B virus X-expressing cells

Virus Research ◽

10.1016/j.virusres.2006.11.007 ◽

2007 ◽

Vol 125 (1) ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Hae-Ryun Um ◽

Won-Chung Lim ◽

Sun-Young Chae ◽

Sun Park ◽

Jeon Han Park ◽

...

Keyword(s):

Hepatitis B Virus ◽

Protein Kinase ◽

Hepatitis B ◽

Cell Survival ◽

Protein Kinase B ◽

B Virus

Download Full-text

NIMA-Related Kinase 6 as an Effective Target Inhibits the Hepatocarcinogenesis and Progression of Hepatocellular Carcinoma

10.21203/rs.3.rs-836610/v1 ◽

2021 ◽

Author(s):

Hao Zhang ◽

Bo Li

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Protein Kinase ◽

Virus Infection ◽

Hepatitis B ◽

Cell Lines ◽

Hepg2 Cells ◽

Control Group ◽

Hepatitis B Virus Infection ◽

B Virus

Abstract BackgroundNever in Mitosis Gene A-Related Kinase (NEK), a member of the cell cycle-dependent protein kinase, encodes a serine/threonine protein kinase involved in mitosis of the G2-M transition period. Eleven NEKs have been identified, and NEK6 is one of them. It has been confirmed that NEK6 is over-expressed in some tumor cell lines. The following study aims to explore the expression of NEK6 in hepatocellular carcinoma (HCC) and the correlation between NEK6 expression and clinical features.MethodsLiver tissues of 79 HCC patients and other patients were obtained during various liver surgeries. Total RNA from these tissue samples was extracted and QPCR was adopted to detect positive expression of NEK6. The correlation between NEK6 expression and the clinical characteristics of HCC was analyzed. The expression of NEK6 in different cell lines (LO-2, HepG2, Li-7, Huh-7, and BEL-7402) was quantified via QPCR. Scratch assay, Transwell assay, and tumor-formation assay in nude mice were used to evaluate the effects of NEK6 on the HCC progression in vitro and in vivo.ResultThe expression of NEK6 was up-regulated in HCC tissue compared with other tissues. The proportion of hepatitis B virus infection in the Nek6 Overexpression group was higher than the Control group (P=0.045). The multiple tumors and bigger tumors (>5 cm) seemed more common in the NEK6 overexpression group (P=0.018, and P=0.037, respectively). Further analysis showed that the overexpression of NEK6 was correlated with hepatitis B virus infection and tumor diameter (P=0.045; P=0.038). The 3-year disease-free survival (DFS) and overall survival (OS) of patients in the NEK6 overexpression group were 14.1% and 33.4%, which were worse than the control group. Tumor size over 5 cm and portal vein invasion were risk factors for both DFS and OS. Nek6 overexpression did not seem to affect the prognosis as a risk factor. Among the human cell lines, the expression of NEK6 was higher in Li-7 cells and HepG2 cells. The migration and invasion capabilities of Li-7 and HepG2 cells were suppressed when the NEK6 expression was down-regulated. The xenograft tumor weight was signiﬁcantly lighter in the shNEK6 group (P < 0.05). ConclusionThe results from the study demonstrated that the expression level of NEK6 was up-regulated in HCC and correlated with the HCC progression, suggesting it might be a clinically valuable biomarker and serve as a potential therapeutic target for treating HCC.

Download Full-text

Hepatitis B virus X protein increases microRNA-21 expression and accelerates the development of hepatoma via the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway

Molecular Medicine Reports ◽

10.3892/mmr.2017.6363 ◽

2017 ◽

Vol 15 (5) ◽

pp. 3285-3291 ◽

Cited By ~ 5

Author(s):

Zhouhua Hou ◽

Jun Quan

Keyword(s):

Hepatitis B Virus ◽

Protein Kinase ◽

Hepatitis B ◽

Signaling Pathway ◽

Protein Kinase B ◽

X Protein ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

B Virus ◽

Phosphoinositide 3 Kinase

Download Full-text

Role of environmental factors in the etiology of hepatocellular carcinoma

Orvosi Hetilap ◽

10.1556/oh.2010.28913 ◽

2010 ◽

Vol 151 (28) ◽

pp. 1132-1136 ◽

Cited By ~ 7

Author(s):

István Tornai

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Environmental Factors ◽

Hepatitis B ◽

Hepatitis A ◽

Virus Hepatitis ◽

B Virus

A krónikus vírushepatitisek jelentik ma a legismertebb okokat a hepatocellularis carcinoma (HCC) kialakulásában. A krónikus B- és C-vírus-hepatitis a májrákok körülbelül 40-50%-át okozza. A nyugati típusú társadalmakban a HCC előfordulása folyamatosan növekvő tendenciát mutat. Az alkohol számít a környezeti tényezők közül a legfontosabbnak, bár az alkoholfogyasztás a legtöbb országban csökken. Ez aláhúzza az egyéb környezeti tényezők fontosságát is. Az elfogyasztott alkoholmennyiséggel egyenes arányban növekszik a cirrhosis és a következményes HCC gyakorisága nőkben és férfiakban egyaránt. A kémiai anyagok közül a legismertebb a Kínában és Afrikában elterjedt aflatoxin, amely a gabonaféléket szennyező mycotoxin. Hasonló területeken endémiás, mint a hepatitis B-vírus, együtt szinergista hatást fejtenek ki. A dohányzás is egyértelműen bizonyított hepatocarcinogen hatással rendelkezik. Ez is jelentősen fokozódik, ha alkoholfogyasztással vagy vírushepatitisszel társul. Társadalmilag talán a legfontosabb az elhízás, a következményes nem alkoholos zsírmáj, illetve steatohepatitis és a 2-es típusú cukorbetegség, amelyek prevalenciája egyre fokozódik. Feltehetően ezek állnak a növekvő HCC-gyakoriság hátterében. Az inzulinrezisztencia és az oxidatív stressz képezik a legfontosabb patogenetikai lépéseket a májsejtkárosodásban. További fontos rizikótényező az orális fogamzásgátlók elterjedt használata. Egyes foglalkozások esetén a tartós szervesoldószer-expozíció is növeli a HCC rizikóját. Védelmet jelenthetnek az antioxidánsok, a szelén, a gyógyszerek közül a statinok és a feketekávé-fogyasztás.

Download Full-text