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HCC signaling pathway

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https://www.readbyqxmd.com/read/28339072/hepatitis-b-virus-x-protein-increases-microrna%C3%A2-21-expression-and-accelerates-the-development-of-hepatoma-via-the-phosphatase-and-tensin-homolog-phosphoinositide-3%C3%A2-kinase-protein-kinase-b-signaling-pathway
#1
Zhouhua Hou, Jun Quan
Hepatitis B virus (HBV) X protein (HBx) is a key regulatory protein that is involved in HBV infection, replication and carcinogenesis of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of HBx in the progression and metastasis of liver cancer cells and to determine the underlying molecular mechanism of HBx in metastatic liver cancer cells. HBx protein expression was detected by western blot analysis, and microRNA (miR)‑21 levels were determined by reverse transcription‑quantitative polymerase chain reaction in the highly metastatic MHCC‑97H low metastatic MHCC‑97L and SMMC‑7721 liver cancer cell lines...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339069/transglutaminase-2-is-upregulated-in-primary-hepatocellular-carcinoma-with-early-recurrence-as-determined-by-proteomic-profiles
#2
Hiromi Yamaguchi, Kazumichi Kuroda, Masahiko Sugitani, Tadatoshi Takayama, Kiyoshi Hasegawa, Mariko Esumi
The mechanism of early recurrence of hepato-cellular carcinoma (HCC) is not well understood. To examine whether early intrahepatic metastasis of HCC can be determined by the reliable molecular characteristics of the primary HCC, we focused on early-stage tumors of primary and solitary HCC cases. Proteomic differences were investigated between two groups, 11 early (recurrence within 12 months) and 10 late (no recurrence within 48 months) HCC cases, using two-dimensional fluorescence difference gel electrophoresis...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28337261/glutathione-s-transferase-a-4-gsta4-suppresses-tumor-growth-and-metastasis-of-human-hepatocellular-carcinoma-by-targeting-akt-pathway
#3
Chang Jun Liu, Jin Hui Yang, Fei Zhou Huang, Wan Pin Nie, Chu Ping Liu, Xian Hai Mao, Xin Min Yin, Xian Bo Shen, Chuang Peng, Mei Fu Chen, Bo Jiang, Xun Yang Liu, Jin Shu Wu
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Up-regulation of glutathione-s-transferase A 4 (GSTA4) is associated with poor prognosis of HCC, but its functional mechanism in HCC remains unclear. In this study, we investigated the roles of GSTA4 in tumor growth and metastasis of HCC and found that GSTA4 was frequently up-regulated in HCC tissues. Through gain- and loss-of-function studies, GSTA4 was demonstrated to significantly regulate cell proliferation, migration, and invasion in vitro...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#4
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334716/downregulation-of-ubap2l-inhibits-the-epithelial-mesenchymal-transition-via-snail1-regulation-in-hepatocellular-carcinoma-cells
#5
Tao Ye, Jing Xu, Ling Du, Wenhui Mo, Yiming Liang, Jinglin Xia
BACKGROUND/AIMS: Dysregulation of ubiquitin-associated protein 2-like (UBAP2L) has been reported in tumors, but its role in hepatocellular carcinoma (HCC) progression is unclear. METHODS: The expression levels of UBAP2L in HCC tissues and HCC cell lines were detected by western blot and quantitative real-time (qRT) PCR. The effects of UBAP2L expression on HCC cell biological traits, including migration and invasion, were investigated by wound healing assay and matrigel transwell assay...
March 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28333142/hydrogen-sulfide-promotes-autophagy-of-hepatocellular-carcinoma-cells-through-the-pi3k-akt-mtor-signaling-pathway
#6
Shanshan S Wang, Yuhan H Chen, Ning Chen, Lijun J Wang, Dexi X Chen, Honglei L Weng, Steven Dooley, Huiguo G Ding
Hydrogen sulfide (H2S), in its gaseous form, plays an important role in tumor carcinogenesis. This study investigated the effects of H2S on the cell biological functions of hepatocellular carcinoma (HCC). HCC cell lines, HepG2 and HLE, were treated with NaHS, a donor of H2S, and rapamycin, a classic autophagy inducer, for different lengths of time. Western blotting, immunofluorescence, transmission electron microscopy (TEM), scratch assay, CCK-8 and flow cytometric analysis were carried out to examine the effects of H2S on HCC autophagy, cell behavior and PI3K/Akt/mTOR signaling...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28328801/influence-of-polymorphisms-in-the-wnt-%C3%AE-catenin-pathway-genes-on-hepatocellular-carcinoma-risk-in-a-chinese-han-population
#7
Qing-Min Li, Feng-Qin Zhang, Ya-Feng Li, Qing-Jie Xian, Yan-Qiang Zhang, Peng Li
The Wnt/β-catenin pathway plays a vital role in initiating and sustaining hepatocellular carcinoma (HCC). However, few studies have investigated polymorphisms in the Wnt/β-catenin signaling pathway genes in the Chinese Han population. The aim of the present retrospective study was to investigate the correlations between polymorphisms of the Wnt/β-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression.Twenty tagging single nucleotide polymorphisms were chosen from HapMap data and genotyped in 320 patients with HCC, 320 chronic hepatitis B virus (HBV)-infected patients without HCC (N-HCC, including 95 liver cirrhosis, 164 chronic hepatitis B, and 61 asymptomatic HBV carriers), and 320 healthy controls...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28323861/overexpression-of-c-jun-contributes-to-sorafenib-resistance-in-human-hepatoma-cell-lines
#8
Yuki Haga, Tatsuo Kanda, Masato Nakamura, Shingo Nakamoto, Reina Sasaki, Koji Takahashi, Shuang Wu, Osamu Yokosuka
BACKGROUND: Despite recent advances in treatment strategies, it is still difficult to cure patients with hepatocellular carcinoma (HCC). Sorafenib is the only approved multiple kinase inhibitor for systemic chemotherapy in patients with advanced HCC. The majority of advanced HCC patients are resistant to sorafenib. The mechanisms of sorafenib resistance are still unknown. METHODS: The expression of molecules involved in the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma cell lines was examined in the presence or absence of sorafenib...
2017: PloS One
https://www.readbyqxmd.com/read/28322443/all-trans-retinoic-acid-ameliorates-hepatic-stellate-cell-activation-via-suppression-of-thioredoxin-interacting-protein-expression
#9
Hiroki Shimizu, Toshiaki Tsubota, Keita Kanki, Goshi Shiota
Activation of hepatic stellate cells (HSCs) is the effector factor of hepatic fibrosis and hepatocellular carcinoma (HCC) development. Accumulating evidence suggests that retinoic acids (RAs), derivatives of vitamin A, contribute to prevention of liver fibrosis and carcinogenesis, however, regulatory mechanisms of RAs still remain exclusive. To elucidate RA signaling pathway, we previously performed a genome-wide screening of RA-responsive genes by in silico analysis of RA-response elements, and identified 26 RA-responsive genes...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28319061/ccdc178-promotes-hepatocellular-carcinoma-metastasis-through-modulation-of-anoikis
#10
X Hu, Y Zhao, L Wei, B Zhu, D Song, J Wang, L Yu, J Wu
Hepatocellular carcinoma (HCC) is one of the most malignant tumors with high rate of recurrence and metastasis. Coiled-coil domain-containing protein 178 (CCDC178) has been reported to be mutated in HCC, whereas its role in physiological and pathologic process, including in human cancer, remains largely unknown. Here, we found that CCDC178 is upregulated in HCC tissues and its overexpression is correlated with pathological stage (P=0.003). CCDC178 deficiency reduced the anchorage-independent growth and anoikis resistance of HCC cells, and inhibited the HCC metastasis in vivo...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28297806/-research-advances-in-the-pathogenesis-of-non-alcoholic-fatty-liver-disease-associated-liver-cancer
#11
W Huang, X X Zhang
Nonalcoholic fatty fiver disease (NAFLD) is one of the most common causes of chronic liver disease in clinical practice. It develops from simple fatty liver, nonalcoholic fatty hepatitis to liver fibrosis which may develop liver cirrhosis and result in hepatocellular carcinoma(HCC) eventually. Although studies show that many cell signaling pathways, genes and cell factors are involved in the progression and development of NAFLD related HCC, the exact mechanism underling the pathogenesis of NAFLD-HCC remains poorly understand...
February 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in-vitro-and-in-mice-by-inhibiting-cdc37-signaling
#12
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
March 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28283039/hepatitis-c-virus-ns3-protein-enhances-hepatocellular-carcinoma-cell-invasion-by-promoting-ppm1a-ubiquitination-and-degradation
#13
Yali Zhou, Yan Zhao, Yaoying Gao, Wenjun Hu, Yan Qu, Ning Lou, Ying Zhu, Xiaoping Zhang, Hongmei Yang
BACKGROUND: Growing evidence suggests that hepatitis C virus (HCV) contributes to hepatocellular carcinoma (HCC) by directly modulating oncogenic signaling pathways. Protein phosphatase magnesium-dependent 1A (PPM1A) has recently emerged as an important tumor suppressor as it can block a range of tumor-centric signaling pathways through protein dephosphorylation. However, the role and regulatory mechanisms of PPM1A in HCV-infected cells have not been reported. METHODS: Total, cytoplasmic, and nuclear PPM1A protein after HCV infection or overexpression of HCV nonstructural protein 3 (NS3) were detected by western blotting...
March 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28282856/hepatitis-b-virus-x-protein-stimulates-proliferation-wound-closure-and-inhibits-apoptosis-of-huh-7-cells-via-cdc42
#14
Yongru Xu, Yingzi Qi, Jing Luo, Jing Yang, Qi Xie, Chen Deng, Na Su, Wei Wei, Deshun Shi, Feng Xu, Xiangping Li, Ping Xu
Chronic hepatitis B virus (HBV) infection has been considered as the major cause of hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) has been reported to be oncogenic. The underlying mechanisms of HBV-related HCC are not fully understood, and the role played by the HBx protein in HBV induced carcinogenesis remains controversial. CDC42, a member of the Rho GTPase family, has been reported to be overexpressed in several different cancers, including HBV-related HCC. However, the specific role of CDC42 in HCC development remains unclear...
March 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28281971/knockdown-of-slc34a2-inhibits-hepatocellular-carcinoma-cell-proliferation-and-invasion
#15
Yanhua Li, Xia Chen, Hong Lu
The gene solute carrier family 34 (sodium phosphate), member 2 (SLC34A2), is a member of the SLC34 family. Increasing evidence suggests that SLC34A2 is involved in the development of many human carcinomas. However, its role in hepatocellular carcinoma (HCC) is still unclear. Therefore, in this study we investigated the role of SLC34A2 in HCC and explored the underlying mechanism. We found that the expression of SLC34A2 is upregulated in HCC cell lines. Knockdown of SLC34A2 obviously inhibited HCC cell proliferation, migration/invasion, and the epithelial-mesenchymal transition (EMT) phenotype...
October 27, 2016: Oncology Research
https://www.readbyqxmd.com/read/28276530/overcoming-sorafenib-evasion-in-hepatocellular-carcinoma-using-cxcr4-targeted-nanoparticles-to-co-deliver-mek-inhibitors
#16
Yunching Chen, Ya-Chi Liu, Yun-Chieh Sung, Rakesh R Ramjiawan, Ts-Ting Lin, Chih-Chun Chang, Kuo-Shyang Jeng, Chiung-Fang Chang, Chun-Hung Liu, Dong-Yu Gao, Fu-Fei Hsu, Annique M Duyverman, Shuji Kitahara, Peigen Huang, Simona Dima, Irinel Popescu, Keith T Flaherty, Andrew X Zhu, Nabeel Bardeesy, Rakesh K Jain, Cyril H Benes, Dan G Duda
Sorafenib is a RAF inhibitor approved for several cancers, including hepatocellular carcinoma (HCC). Inhibition of RAF kinases can induce a dose-dependent "paradoxical" upregulation of the downstream mitogen-activated protein kinase (MAPK) pathway in cancer cells. It is unknown whether "paradoxical" ERK activation occurs after sorafenib therapy in HCC, and if so, if it impacts the therapeutic efficacy. Here, we demonstrate that RAF inhibition by sorafenib rapidly leads to RAF dimerization and ERK activation in HCCs, which contributes to treatment evasion...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28276313/inhibition-of-mmp-2-expression-enhances-the-anti-tumor-effect-of-sorafenib-in-hepatocellular-carcinoma-by-suppressing-pi3k-akt-mtor-pathway
#17
Wenliang Tan, Sicong Zhu, Jun Cao, Lei Zhang, Wenda Li, Kairui Liu, Jinyi Zhong, Changzhen Shang, Yajin Chen
Sorafenib has been globally approved as the standard treatment for patients with advanced Hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited due to tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve the anti-tumor efficiency. Here we demonstrated that expression of MMP-2 positively correlated with the migration ability of HCC cells. Cells with higher MMP-2 expression (SK-HEP-1 cells) were less sensitive to sorafenib than those with lower MMP-2 expression (HepG2 cells)...
March 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/28273636/mir-30b-5p-acts-as-a-tumor-suppressor-repressing-cell-proliferation-and-cell-cycle-in-human-hepatocellular-carcinoma
#18
Xian Qin, Jing Chen, Long Wu, Zhisu Liu
MicroRNAs have been verified to participate in various biological behaviors of different tumors, via multiple signaling pathways. Many kinds of microRNAs in hepatocellular carcinoma have been researched. However, miR-30b-5p hasn't been included. Our study aim at the impacts of miR-30b-5p on HCC and the pathway it mediating. The results showed miR-30b-5p was significant downregulated in HCC tissues and cell lines. With clinical data, we've discovered miR-30b-5p was correlated with several clinical pathological characteristics, such as survival time, tumor size, HBV infected, pathological stage, differentiation and intrahepatic metastasis...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28262728/chemical-or-genetic-pin1-inhibition-exerts-potent-anticancer-activity-against-hepatocellular-carcinoma-by-blocking-multiple-cancer-driving-pathways
#19
Xin-Hua Liao, Arina Li Zhang, Min Zheng, Mei-Qing Li, Champ Peng Chen, Huijuan Xu, Qing-Song Chu, Dayun Yang, Wenxian Lu, Ting-Fen Tsai, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant cancers with high inter- and intra-tumor heterogeneity. A central common signaling mechanism in cancer is proline-directed phosphorylation, which is further regulated by the unique proline isomerase Pin1. Pin1 is prevalently overexpressed in human cancers including ~70% of HCC, and promotes tumorigenesis by activating multiple cancer-driving pathways. However, it was challenging to evaluate the significance of targeting Pin1 in cancer treatment until the recent identification of all-trans retinoic acid (ATRA) as a Pin1 inhibitor...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259942/high-expression-of-rbm8a-predicts-poor-patient-prognosis-and-promotes-tumor-progression-in-hepatocellular-carcinoma
#20
Rong Liang, Yan Lin, Jia-Zhou Ye, Xue-Xin Yan, Zhi-Hui Liu, Yong-Qiang Li, Xiao-Ling Luo, Hai-Hong Ye
Hepatocellular carcinoma (HCC) is a huge threat for human health worldwide. As a complicated tumor, the molecular basis for HCC development especially metastasis requires exploration. Although RNA binding motif (RBM) proteins are closely related to various cancers, the clinical importance and underlying mechanisms of RBM8A in HCC remain elusive. In this study, we found that RBM8A was highly expressed in HCC tumor tissues compared to normal liver tissues. Overexpression of RBM8A was associated with HbsAg and Edmondson pathological grading...
February 15, 2017: Oncology Reports
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