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HCC signaling pathway

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https://www.readbyqxmd.com/read/29050265/reactive-oxygen-species-dependent-phosphorylation-of-the-liver-kinase-b1-amp-activated-protein-kinase-acetyl-coa-carboxylase-signaling-is-critically-involved-in-apoptotic-effect-of-lambertianic-acid-in-hepatocellular-carcinoma-cells
#1
Arong Jeong, Ju-Ha Kim, Hyo-Jung Lee, Sung-Hoon Kim
Though lambertianic acid (LA) is reported to have hypolipidemic activity in liver, its underlying anticancer mechanism is poorly understood so far. Thus, in the present study, apoptotic mechanism of LA was elucidated in HepG2 and SK-Hep1 hepatocellular carcinoma (HCC) cells. Here LA increased cytotoxicity, sub-G1 population and Annexin V/PI positive cells in two HCC cells. Also, LA cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), activated phosphorylation of liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK)/ acetyl-CoA carboxylase (ACC) pathway and also suppressed antiapoptotic proteins such as phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and the expression of B cell lymphoma-2 (Bcl-2)/ B-cell lymphoma-extra large (Bcl-xL) and cyclooxygenase-2 (COX-2) in two HCC cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048612/regulation-of-erk-and-akt-pathways-by-hepatitis%C3%A2-b-virus%C3%A2-x-protein-via-the-notch1-pathway-in-hepatocellular-carcinoma
#2
Bo Liao, Honghao Zhou, Huifang Liang, Changhai Li
Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including the Notch1 pathway in HCC. In this study, we found that Notch1 was highly expressed in HCC, especially in large HCCs. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 cells than that in HepG2 cells. HBx activated the Notch1 pathway in HepG2...
September 15, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29042961/the-long-non-coding-rna-ak023948-enhances-tumor-progression-in-hepatocellular-carcinoma
#3
Bailiang Ye, Bingren Hu, Zhihai Zheng, Ru Zheng, Yixiong Shi
The long non-coding RNAs (lncRNAs) have been demonstrated to play pivotal roles in a broad range of processes including tumor biology. However, the exact contributions of lncRNAs to hepatocellular carcinoma (HCC) remain poorly defined. In current study, we have unraveled a novel function of AK023948 in HCC. We found that AK023948 was substantially upregulated in tumor tissues. Meanwhile, higher AK023948 expression correlated with poor survival. Upregulation of AK023948 expression can promote HepG2 and Hep3B proliferation and invasion in in vitro experiments...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29040995/role-of-immune-checkpoint-blockade-in-the-treatment-for-human-hepatocellular-carcinoma
#4
Naoshi Nishida, Masatoshi Kudo
With the development of molecular targeting therapy, several treatment options for advanced hepatocellular carcinoma (HCC) have become available in cases where curative and other palliative treatments, such as radiofrequency ablation, surgical resection, and transarterial chemoembolization, are not applicable. However, with the detection of a variety of mutations in cancer-related genes in a single tumor, molecular heterogeneity is commonly observed in HCC. Therefore, mutations in the major cellular signaling pathways underlie the development of resistance to molecular targeting agents...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29039502/long-non%C3%A2-coding-rna-hottip-promotes-hepatocellular-carcinoma-tumorigenesis-and-development-a-comprehensive-investigation-based-on-bioinformatics-qrt%C3%A2-pcr-and-meta%C3%A2-analysis-of-393-cases
#5
Yu Zhang, Jia-Cheng Huang, Kai-Teng Cai, Xi-Bing Yu, You-Rong Chen, Wen-Ya Pan, Ze-Liang He, Jun Lv, Zhen-Bo Feng, Gang Chen
HOTTIP functions as an independent biomarker in multiple cancers. However, the role of HOTTIP in hepatocellular carcinoma (HCC) remains unclear. In this study, we sought to investigate the HOTTIP expression in HCC and normal liver. We combined quantitative reverse transcription-polymerase chain reactions (qRT‑PCR), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), Multi Experiment Matrix (MEM) and Oncomine database to assess the clinical role and the potential molecular mechanism of HOTTIP in HCC...
October 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29038587/cell-surface-major-vault-protein-promotes-cancer-progression-through-harboring-mesenchymal-and-intermediate-circulating-tumor-cells-in-hepatocellular-carcinomas
#6
Hyun Min Lee, Jae Won Joh, Se-Ri Seo, Won-Tae Kim, Min Kyu Kim, Hong Seo Choi, So Young Kim, Young-Joo Jang, Dong Hyun Sinn, Gyu Seong Choi, Jong Man Kim, Choon Hyuck David Kwon, Hee Jin Chang, Dae Shick Kim, Chun Jeih Ryu
Circulating tumor cells (CTCs) play a major role in the metastasis and recurrence of hepatocellular carcinoma (HCC). Here, we found that major vault protein (MVP) is expressed on the surface of HCC cells and further induced under stressful environments. MVP knockdown reduces cell proliferation and induces apoptosis in HCC cells. Treatment of HCC cells with anti-MVP antibody (α-MVP) recognizing cell-surface MVP (csMVP) inhibits cell proliferation, migration, and invasion. csMVP-positive HCC cells have a higher clonogenic survival than csMVP-negative HCC cells, and treatment of HCC cells with α-MVP inhibits clonogenic survival, suggesting that csMVP contributes to HCC cell survival, migration, and invasion...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29033906/long-non-coding-rnas-in-hepatitis-c-virus-infected-cells
#7
REVIEW
Marina Barriocanal, Puri Fortes
Hepatitis C virus (HCV) often leads to a chronic infection in the liver that may progress to steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several viral and cellular factors are required for a productive infection and for the development of liver disease. Some of these are long non-coding RNAs (lncRNAs) deregulated in infected cells. After HCV infection, the sequence and the structure of the viral RNA genome are sensed to activate interferon (IFN) synthesis and signaling pathways. These antiviral pathways regulate transcription of several cellular lncRNAs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29033545/downregulation-of-a20-increases-the-cytotoxicity-of-ifn-%C3%AE-in-hepatocellular-carcinoma-cells
#8
Lei Yin, Zheng Fang, Ning-Jia Shen, Ying-He Qiu, Ai-Jun Li, Yong-Jie Zhang
Hepatocellular carcinoma (HCC) is a highly fatal disease mandating development of novel, effective therapeutic strategy. Interferon-gamma (IFN-γ) is a pleiotropic cytokine with immunomodulatory, antiviral, and antitumor effects. Although IFN-γ is a promising antitumor agent, its application is limited by resistance in tumor cells. A20 is a zinc-finger protein that was initially identified as a gene product induced by tumor necrosis factor α in human umbilical vein endothelial cells. In this study, we found that silencing of A20 combined with IFN-γ significantly represses cell viability, and induces apoptosis and cell-cycle arrest in HCC cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29032337/mir-758-3p-suppresses-proliferation-migration-and-invasion-of-hepatocellular-carcinoma-cells-via-targeting-mdm2-and-mtor
#9
Dan Jiang, William Cho, Zhenhao Li, Xiangrong Xu, Yuliang Qu, Zhongjia Jiang, Le Guo, Guangxian Xu
Hepatocelluar carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide and among the leading causes of cancer-related death. Although deregulation of microRNAs has been frequently described in HCC, imperfection is known about the precise molecular mechanisms by which microRNAs modulate the process of tumorogenesis and behavior of cancer cells. In this study, we demonstrated that miR-758-3p could suppress cell proliferation, migration and invasion in hepatocellular carcinoma cells. We screened and identified two novel miR-758-3p targets, MDM2 and mTOR...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29032312/advanced-oxidation-protein-products-induce-s-phase-arrest-of-hepatocytes-via-the-ros-dependent-%C3%AE-catenin-cdk2-mediated-pathway
#10
Shibo Sun, Fang Xie, Xiaoping Xu, Qing Cai, Qifan Zhang, Zhonglin Cui, Yujian Zheng, Jie Zhou
Liver regeneration has important clinical importance in the setting of partial hepatectomy (PH). Following PH, quiescent hepatocytes can reenter cell cycle to restore liver mass. Hepatocyte cell cycle progression, as the basic motivations of liver regeneration, can be disrupted by multiple pathological factors such as oxidative stress. This study aimed to evaluate the role of advanced oxidation protein products (AOPP) in S-phase arrest in hepatocytes. Serum AOPP level were measured during the perioperative period of PH in 33 patients with hepatocellular carcinoma (HCC)...
October 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29031523/6-hydroxy-3-o-methyl-kaempferol-6-o-glucopyranoside-potentiates-the-anti-proliferative-effect-of-interferon-%C3%AE-%C3%AE-by-promoting-activation-of-the-jak-stat-signaling-by-inhibiting-socs3-in-hepatocellular-carcinoma-cells
#11
Orawan Wonganan, Yu-Jiao He, Xiao-Fei Shen, Kanjana Wongkrajang, Apichart Suksamrarn, Guo-Lin Zhang, Fei Wang
Suppressor of cytokine signaling 3 (SOCS3) is a key negative regulator of type I interferon (IFN α/β) signaling. Inhibition of SOCS3 by small molecules may be a new strategy to enhance the efficacy of type I IFN and reduce its side effects. We established a cell-based screening assay using human hepatoma HepG2 cells stably transfected with a plasmid wherein the luciferase reporter activity was propelled by interferon α-stimulated response element (ISRE), which is a motif specifically recognized by type I IFN-induced activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway...
October 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29030911/phosphorylated-erk-is-a-potential-prognostic-biomarker-for-sorafenib-response-in-hepatocellular-carcinoma
#12
Yuelong Liang, Jiang Chen, Qingsong Yu, Tong Ji, Bin Zhang, Junjie Xu, Yi Dai, Yangyang Xie, Hui Lin, Xiao Liang, Xiujun Cai
Sorafenib, the only approved drug for hepatocellular carcinoma, acts as a remarkable inhibitor of Raf serine-threonine kinases. However, Sorafenib is expensive, and clinical experience shows that it is not an effective treatment for many patients. Previous study has demonstrated that phosphorylated ERK (pERK) is a key downstream component in the RAF/MEK/ERK signaling pathway. Here, we investigate whether pERK is a useful biomarker for treating HCC with Sorafenib. In vitro cell viability assays showed that the efficacy of Sorafenib was distinctly different according to the level of pERK...
October 13, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29029515/discovery-of-nkcc1-as-a-potential-therapeutic-target-to-inhibit-hepatocellular-carcinoma-cell-growth-and-metastasis
#13
Yaya Zhou, Wei Sun, Ning Chen, Chen Xu, Xinxin Wang, Kun Dong, Binxue Zhang, Jian Zhang, Ning Hao, Aihua Sun, Handong Wei, Fuchu He, Ying Jiang
Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029500/edg2-enhanced-the-progression-of-hepatocellular-carcinoma-by-lpa-pi3k-akt-mtor-signaling
#14
Meng Xu, Zhikui Liu, Cong Wang, Bowen Yao, Xin Zheng
HCC is the leading type of the malignant liver tumors with the unsatisfied prognosis. Liver resection has been considered as the predominant curative therapy, however, the post-surgical prognostic evaluation remains an urgent problem and the mechanism of HCC metastases has not been understood completely. EDG2 has been found to accelerate tumor progression through mediating different cell pathways, however, it remains unclear about the role of EDG2 on hepatocarcinogenesis. Here, EDG2 expression was found increased notably in HCC tissues by immunohistochemistry compared with adjacent liver tissues and comparison of survival curves revealed that EDG2 upregulation in HCC tissues was associated with the worse prognosis after liver resection...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029483/the-long-noncoding-rna-tug1-acts-as-a-competing-endogenous-rna-to-regulate-the-hedgehog-pathway-by-targeting-mir-132-in-hepatocellular-carcinoma
#15
Jingjing Li, Qinghui Zhang, Xiaoming Fan, Wenhui Mo, Weiqi Dai, Jiao Feng, Liwei Wu, Tong Liu, Sainan Li, Shizan Xu, Wenwen Wang, Xiya Lu, Qiang Yu, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Ling Xu, Chuanyong Guo
Emerging evidence shows that the Hedgehog pathway and the long noncoding RNA TUG1 play pivotal roles in cell proliferation, migration, and invasion in tumors. However, the mechanism underlying the effect of TUG1 and the Hedgehog pathway in hepatoma remains undefined. In the present study, we showed that the expression of TUG1 was negatively correlated with that of microRNA (miR)-132, and depletion of TUG1 inhibited the activation of the Hedgehog pathway in vitro and in vivo. We showed that TUG1 functions as a competing endogenous (ceRNA) by competing with miR-132 for binding to the sonic hedgehog protein in HCC, thereby suppressing the activation of Hedgehog signaling and its tumorigenic effect...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029413/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#16
Ming-Hung Hu, Li-Ju Chen, Yen-Lin Chen, Ming-Shen Tsai, Chung-Wai Shiau, Tzu-I Chao, Chun-Yu Liu, Jia-Horng Kao, Kuen-Feng Chen
Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027943/low-grade-dysplastic-nodules-revealed-as-the-tipping-point-during-multistep-hepatocarcinogenesis-by-dynamic-network-biomarkers
#17
Lina Lu, Zhonglin Jiang, Yulin Dai, Luonan Chen
Hepatocellular carcinoma (HCC) is a complex disease with a multi-step carcinogenic process from preneoplastic lesions, including cirrhosis, low-grade dysplastic nodules (LGDNs), and high-grade dysplastic nodules (HGDNs) to HCC. There is only an elemental understanding of its molecular pathogenesis, for which a key problem is to identify when and how the critical transition happens during the HCC initiation period at a molecular level. In this work, for the first time, we revealed that LGDNs is the tipping point (i...
October 13, 2017: Genes
https://www.readbyqxmd.com/read/29027712/upregulation-of-ube2q1-via-gene-copy-number-gain-in-hepatocellular-carcinoma-promotes-cancer-progression-through-%C3%AE-catenin-egfr-pi3k-akt-mtor-signaling-pathway
#18
Bin Zhang, Chao Deng, Lei Wang, Fan Zhou, Shu Zhang, Wei Kang, Ping Zhan, Juan Chen, Shanshan Shen, Huimin Guo, Ming Zhang, Yi Wang, Feng Zhang, Wei Zhang, Jiangqiang Xiao, Bo Kong, Helmut Friess, Yuzheng Zhuge, Hongli Yan, Xiaoping Zou
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and represents a highly malignant tumor with a poor prognosis. Therapeutic modalities for HCC are limited and generally ineffective. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and has been shown to be overexpressed in various types of cancers including HCC. How UBE2Q1 contributes to hepatocarcinogenesis remains unknown. Here, we show that UBE2Q1 is up-regulated in HCC cell lines and in a subset of human HCC tissues. Up-regulation of UBE2Q1 in primary HCC tumors was significantly correlated with shorter overall survival and disease-free survival...
October 13, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29025272/gankyrin-a-novel-promising-therapeutic-target-for-hepatocellular-carcinoma
#19
Parvin Zamani, Maryam Matbou Riahi, Amir Abbas Momtazi-Borojeni, Khadijeh Jamialahmadi
Hepatocellular carcinoma (HCC) is known as fifth common malignancies and third common cause of cancer-related death worldwide. The identification of various mechanisms which are involved in hepatocarcinogenesis contributes in finding a variety of cellular and molecular targets for HCC diagnosis, prevention and therapy. Among various identified targets in HCC pathogenesis, Gankyrin is a crucial oncoprotein that is up-regulated in HCC and plays a pivotal role in the initiation and progression of the HCC. Oncogenic role of Gankyrin has been found to stem from inhibition of two ubiquitous tumour suppressor proteins, retinoblastoma protein (pRb) and P53, and also modulation of several vital cellular signalling pathways including Wnt/β-Catenin, NF-κB, STAT3/Akt, IL-1β/IRAK-1 and RhoA/ROCK...
October 12, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29022911/the-level-of-caveolin-1-expression-determines-response-to-tgf-%C3%AE-as-a-tumour-suppressor-in-hepatocellular-carcinoma-cells
#20
Joaquim Moreno-Càceres, Daniel Caballero-Díaz, Zeribe Chike Nwosu, Christoph Meyer, Judit López-Luque, Andrea Malfettone, Raquel Lastra, Teresa Serrano, Emilio Ramos, Steven Dooley, Isabel Fabregat
Hepatocellular carcinoma (HCC) is a heterogeneous tumour associated with poor prognostic outcome. Caveolin-1 (CAV1), a membrane protein involved in the formation of caveolae, is frequently overexpressed in HCC. Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine having a dual role in hepatocarcinogenesis: inducer of apoptosis at early phases, but pro-tumourigenic once cells acquire mechanisms to overcome its suppressor effects. Apoptosis induced by TGF-β is mediated by upregulation of the NADPH oxidase NOX4, but counteracted by transactivation of the epidermal growth factor receptor (EGFR) pathway...
October 12, 2017: Cell Death & Disease
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