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https://www.readbyqxmd.com/read/28430373/a-five-mirna-expression-signature-predicts-survival-in-hepatocellular-carcinoma
#1
Gang Liu, Hui Wang, Jin-Dong Fu, Jing-Ying Liu, Ai-Guo Yan, Yan-Yan Guan
The aim of this study was to identify a microRNA (miRNA) expression signature for predicting HCC (hepatocellular carcinoma) survival. A total of 322 HCC patients in The Cancer Genome Atlas (TCGA) database were randomly divided into training and testing set. miRNAs, associated with survival time in the training set, were identified by using univariate Cox regression analysis. The risk score was formulated based on the expression levels of these miRNAs. Then the miRNA signature was validated in testing set through Kaplan-Meier analysis and log-rank test...
April 21, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28429652/atypical-regulators-of-wnt-%C3%AE-catenin-signaling-as-potential-therapeutic-targets-in-hepatocellular-carcinoma
#2
Jianxiang Chen, Muthukumar Rajasekaran, Kam M Hui
Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428278/oncogenic-role-of-snd1-in-development-and-progression-of-hepatocellular-carcinoma
#3
Nidhi Jariwala, Devaraja Rajasekaran, Rachel G Mendoza, Xue-Ning Shen, Ayesha Siddiq, Maaged Akiel, Chadia L Robertson, Mark A Subler, Jolene Windle, Paul B Fisher, Arun J Sanyal, Devanand Sarkar
SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-kappaB signaling pathways in promoting TIC formation in Alb/SND1 mice...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427193/targeting-high-aurora-kinases-expression-as-an-innovative-therapy-for-hepatocellular-carcinoma
#4
Fuchen Liu, Guangyong Wang, Xiaoqiang Wang, Zhihui Che, Wei Dong, Xinggang Guo, Zhenguang Wang, Ping Chen, Daisen Hou, Qi Zhang, Wenli Zhang, Yida Pan, Dongqin Yang, Hui Liu
The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, however, it remains unknown whether Aurora A and B overexpressed concomitantly and its clinical significance in hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co-overexpression (Aurora AHBH), associated with the worst prognosis, was an independent predictor for the survival. Importantly, with the lower IC50 and stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor of Aurora kinases, which induced YAP (Yes-associated protein) reduction and resulted in P21 accumulation, significantly promoted the polyploidy (> 4N) formation and apoptosis in HCC...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423650/mir-425-5p-promotes-invasion-and-metastasis-of-hepatocellular-carcinoma-cells-through-scai-mediated-dysregulation-of-multiple-signaling-pathways
#5
Feng Fang, Tianqiang Song, Ti Zhang, Yunlong Cui, Gewen Zhang, Qingqing Xiong
MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC) progression and are key determinants of prognosis. In this study, we found that miR-425-5p was elevated in HCC and correlated with poor prognostic clinicopathological features and low post-operative long-term survival. Multivariate survival analysis indicated that miR-425-5p expression was an independent risk factor for overall and disease-free survival. Interestingly, miR-425-5p promoted invasion and metastasis by HCC cells, but not HCC cell proliferation or apoptosis in vitro...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423613/secreted-grp78-activates-egfr-src-stat3-signaling-and-confers-the-resistance-to-sorafeinib-in-hcc-cells
#6
Rui Li, Gu Yanjiao, He Wubin, Wang Yue, Huang Jianhua, Zheng Huachuan, Su Rongjian, Luan Zhidong
Acquired resistance is a common phenomenon for HCC patients who undergone sorafenib treatment, however the mechanism by which acquired resistance develops remains elusive. In this study, we found that GRP78 could be detected in the serum samples of HCC patients and the conditional medium of multiple HCC cell lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed that secreted GRP78 facilitated the proliferation and inhibited the apoptosis induced by sorafenib both in HCC cell lines and in tumor xenografts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423575/activated-notch-signaling-augments-cell-growth-in-hepatocellular-carcinoma-via-up-regulating-the-nuclear-receptor-nr4a2
#7
Bo Zhu, Lichun Sun, Wei Luo, Min Li, David H Coy, Long Yu, Wenbo Yu
Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional therapies are limited due to the human liver being such a unique organ and easily showing side-effects. The unclear molecular mechanisms are tough challenges for scientists searching for new and effective anti-HCC targeting drugs. We identified that the nuclear receptor NR4A2 is a novel oncogene in HCC progression. In this study, we show that NR4A2 and the notch recceptor Notch1 were expressed highly in primary HCC tissues and immortal HCC cells by using qPCR, western blot and immuno-histochemistry assays...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419966/small-nucleolar-rna-aca11-promotes-proliferation-migration-and-invasion-in-hepatocellular-carcinoma-by-targeting-the-pi3k-akt-signaling-pathway
#8
Long Wu, Junying Zheng, Ping Chen, Quanyan Liu, Yufeng Yuan
Emerging evidence suggests that tumorigenesis involves dysregulation of small nucleolar RNAs (snoRNAs). However, the role of small nucleolar RNA ACA11 (ACA11) in the development of hepatocellular carcinoma (HCC) remains unknown. Expression of ACA11 was measured using quantitative RT-PCR in 92 HCC specimens and 7 HCC cell lines. We found that ACA11 expression was significantly upregulated in HCC tissues and hepatoma cell lines. This upregulation of ACA11 in HCC tumors was significantly associated with histological grade, HBV infection, Barcelona Clinic Liver Cancer stage, portal vein tumor thrombus and poorer patient survival...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28417539/usp22-mediates-the-multidrug-resistance-of-hepatocellular-carcinoma-via-the-sirt1-akt-mrp1-signaling-pathway
#9
Sunbin Ling, Jie Li, Qiaonan Shan, Haojiang Dai, Di Lu, Xue Wen, Penghong Song, Haiyang Xie, Lin Zhou, Jimin Liu, Xiao Xu, Shusen Zheng
Drug treatments for hepatocellular carcinoma (HCC) often fail because of multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem cells (CSC), which are able to self-renew and differentiate, have recently been shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22 (USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we found that modified USP22 levels were responsible for the altered drug-resistant phenotype of BEL7402 and BEL/FU cells...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28416267/molecular-mechanisms-and-targets-of-therapy-for-hepatocellular-carcinoma
#10
REVIEW
Vivian Klungboonkrong, Dola Das, Gordon McLennan
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC develops through a multistep process that involves the local tumor microenvironment, intracellular signaling pathways, and altered metabolic system that allows the cancer proliferation. Understanding the mechanisms of tumor development and progression is critical to developing improved therapies aimed at better survival. This article reviews the molecular mechanisms of HCC development and highlights the potential therapeutic targets for treatments...
April 14, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28415775/adverse-genomic-alterations-and-stemness-features-are-induced-by-field-cancerization-in-the-microenvironment-of-hepatocellular-carcinomas
#11
Darko Castven, Michael Fischer, Diana Becker, Stefan Heinrich, Jesper B Andersen, Dennis Strand, Martin F Sprinzl, Susanne Strand, Carolin Czauderna, Stefanie Heilmann-Heimbach, Stephanie Roessler, Arndt Weinmann, Marcus A Wörns, Snorri S Thorgeirsson, Peter R Galle, Matthias S Matter, Hauke Lang, Jens U Marquardt
Hepatocellular Carcinoma (HCC) commonly develops in chronically damaged liver tissues. The resulting regenerative and inflammatory processes create an adverse milieu that promotes tumor-initiation and progression. A better understanding of the hepatic tumor-microenvironment interaction might infer profound therapeutic implications.Integrative whole genome and transcriptome analyses of different tumor regions, the invasive tumor border and tumor-surrounding liver (SL) were performed to identify associated molecular alterations and integrated with our existing HCC database...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415588/smad-inhibitor-induces-csc-differentiation-for-effective-chemosensitization-in-cyclin-d1-and-tgf-%C3%AE-smad-regulated-liver-cancer-stem-cell-like-cells
#12
Wei Xia, Chung Mau Lo, Randy Y C Poon, Tan To Cheung, Albert C Y Chan, Lin Chen, Sitian Yang, George S W Tsao, Xiao Qi Wang
Understanding cancer stem cell (CSC) maintenance pathways is critical for the development of CSC-targeting therapy. Here, we investigated the functional role of the cyclin D1-dependent activation of Smad2/3 and Smad4 in hepatocellular carcinoma (HCC) CSCs and in HCC primary tumors. Cyclin D1 sphere-derived xenograft tumor models were employed to evaluate the therapeutic effects of a Smad inhibitor in combination with chemotherapy. Cyclin D1 overexpression confers stemness properties by enhancing single sphere formation, enhancing the CD90+ and EpCAM+ population, increasing stemness gene expression, and increasing chemoresistance...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396836/down-regulation-of-mir-146a-5p-and-its-potential-targets-in-hepatocellular-carcinoma-validated-by-a-tcga-and-geo-based-study
#13
Xin Zhang, Zhi-Hua Ye, Hai-Wei Liang, Fang-Hui Ren, Ping Li, Yi-Wu Dang, Gang Chen
Our previous research has demonstrated that miR-146a-5p is down-regulated in hepatocellular carcinoma (HCC) and might play a tumor-suppressive role. In this study, we sought to validate the decreased expression with a larger cohort and to explore potential molecular mechanisms. GEO and TCGA databases were used to gather miR-146a-5p expression data in HCC, which included 762 HCC and 454 noncancerous liver tissues. A meta-analysis of the GEO-based microarrays, TCGA-based RNA-seq data, and additional qRT-PCR data validated the down-regulation of miR-146a-5p in HCC and no publication bias was observed...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28394926/gp73-represses-host-innate-immune-response-to-promote-virus-replication-by-facilitating-mavs-and-traf6-degradation
#14
Xuewu Zhang, Chengliang Zhu, Tianci Wang, Hui Jiang, Yahui Ren, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28390038/integrative-transcriptome-analysis-of-liver-cancer-profiles-identifies-upstream-regulators-and-clinical-significance-of-acsm3-gene-expression
#15
Ramani Gopal, Karthikeyan Selvarasu, Ponmathi Panneer Pandian, Kumaresan Ganesan
PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common human malignancies. It has frequently been associated with metabolic perturbations and liver damages. Various members of the family of acyl-CoA synthetases are known to be involved in the production of bioactive fatty acids, and altered expression of its encoding genes has been found to be involved in metabolic perturbations. For the development of novel diagnostic and therapeutic HCC options, a fundamental understanding of the mechanisms associated with the deregulation of candidate genes involved in metabolic perturbation is required...
April 7, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28385009/inhibitory-effects-of-resveratrol-on-hepatitis-b-virus-x-protein-hbx-induced-hepatocellular-carcinoma-hcc
#16
Seungmo Park, Jihae Lim, Jong Rhan Kim, Seongbeom Cho
Liver cancer occurs very frequently worldwide and hepatocellular carcinoma (HCC) accounts for more than 80% of total primary liver cancer cases. Here, the anticarcinogenic effects of resveratrol against hepatitis B virus (HBV)-induced HCC were investigated using HBV X-protein-overexpressing Huh7 (Huh7-HBx) human hepatoma cells. MTT assay showed that resveratrol decreased cell viability. Fluorescence-activated cell sorter analysis showed that it induced G1 cell cycle arrest without increasing the sub-G1 phase cell population...
April 6, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28384913/study-of-dickkopf-1-dkk-1-gene-expression-in-hepatocellular-carcinoma-patients
#17
Mona Watany, Rehab Badawi, Walaa Elkhalawany, Sherief Abd-Elsalam
INTRODUCTION: Hepatocellular Carcinoma (HCC) is the sixth most common cancer in the world. Dickkopf -1 (DKK-1) protein is a new biomarker used in conjunction with Alpha Fetoprotein (AFP) to differentiate HCC from "non-malignant" liver disease. DKK-1 is an inhibitor of Wnt/β-catenin signaling pathway which is involved in embryogenesis and has been implicated in tumorigenesis in many tissues. AIM: To investigate the level of DKK-1 gene expression in the peripheral blood of patients with HCC who had a history of Hepatitis C Virus (HCV) and schistosomal infections...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28377178/targeting-kdm1a-attenuates-wnt-%C3%AE-catenin-signaling-pathway-to-eliminate-sorafenib-resistant-stem-like-cells-in-hepatocellular-carcinoma
#18
Mengxi Huang, Cheng Chen, Jian Geng, Dong Han, Tao Wang, Tao Xie, Liya Wang, Ye Wang, Chunhua Wang, Zengjie Lei, Xiaoyuan Chu
Use of the tyrosine kinase inhibitor sorafenib in patients with advanced hepatocellular carcinoma (HCC) is often hindered by the development of resistance, which has been recently shown to be associated with the emergence of a cancer stem cell (CSC) subpopulation. However, it remains largely unknown whether epigenetic mechanisms, especially histone posttranslational modifications, are causally linked to the maintenance of stem-like properties in sorafenib-resistant HCC. In this study, we report that the activity of lysine-specific histone demethylase 1A (KDM1A or LSD1) is required for the emergence of cancer stem cells following prolonged sorafenib treatment...
April 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28375585/down-regulation-of-talin1-promotes-hepatocellular-carcinoma-progression-via-activation-of-the-erk1-2-pathway
#19
Chen Peijuan, Lei Ling, Wang Jian, Zou Xuejing, Zhang Dongyan, Deng Ling, Wu Dehua
Talin1 is an adaptor protein that conjugates integrins to the cytoskeleton and regulates integrins and focal adhesion signaling. Several studies have found that Talin1 is over-expressed in several tumor types and promotes tumor progression. However, the explicit role of Talin1 in hepatocellular carcinoma (HCC) progression is still unclear and its functional mechanism remains largely unknown. In this study, we showed a trend of gradually decreasing expression of Talin1 from normal liver tissues to hepatocirrhosis, liver hyperplasia, the corresponding adjacent non-tumor, primary HCC and eventually metastatic foci, indicating that Talin1 maybe correlate with HCC initiation to progression...
April 4, 2017: Cancer Science
https://www.readbyqxmd.com/read/28370287/a-functional-mtorc1-signaling-is-indispensable-for-c-myc-driven-hepatocarcinogenesis
#20
Pin Liu, Mengmeng Ge, Junjie Hu, Xiaolei Li, Li Che, Kun Sun, Lili Cheng, Yuedong Huang, Maria G Pilo, Antonio Cigliano, Giovanni M Pes, Rosa M Pascale, Stefania Brozzetti, Gianpaolo Vidili, Alberto Porcu, Antonio Cossu, Giuseppe Palmieri, Maria C Sini, Silvia Ribback, Frank Dombrowski, Junyan Tao, Diego F Calvisi, Ligong Chen, Xin Chen
Amplification and/or activation of the c-Myc protooncogene is one of the leading genetic events along hepatocarcinogenesis. The oncogenic potential of c-Myc has been proven experimentally by the finding that its overexpression in the mouse liver triggers tumor formation. However, the molecular mechanism whereby c-Myc exerts its oncogenic activity in the liver remains poorly understood. Here, we demonstrate that the mammalian target of rapamycin complex 1 (mTORC1) cascade is activated and necessary for c-Myc dependent hepatocarcinogenesis...
March 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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