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HCC signaling pathway

Bing Tian, Zhen-Ning Lu, Xiu-Li Guo
Hepatocellular carcinoma (HCC) chemoresistance, which is regarded as a kind of stress management reaction to chemotherapy drugs, severely hinders the therapy outcomes of HCC treatment. Stress management is generally achieved by activating certain signal pathways and chemical factors, among which, nuclear factor-E2-related factor2 (Nrf2) is a key factor in HCC chemoresistance formation. Nrf2 is a nuclear factor that coordinates the induction and expression of a battery of genes encoding cytoprotective proteins when participating in the Nrf2antioxidant response element (Nrf2/ARE) pathway, which is one of the most important intracellular antioxidant stress pathways...
December 6, 2017: Chemico-biological Interactions
Ji Wang, Wei Chen, Weiwei Wei, Jianying Lou
The prognostic biomarkers and potential therapy targets are urgently needed in hepatocellular carcinoma (HCC). In this article, we report the expression of TUBA1C was significantly increased in HCC on mRNA and protein level, and this finding was further validated in another two independent datasets. Survival analysis was also implemented on these three datasets, and TUBA1C high expression group was detected to have relative shorter survival time. Furthermore, the metastatic ability is increased along with TUBA1C abundance, according to protein abundance evaluation of normal-tumor-portal vein tumor thrombus pairs, and mRNA comparison between metastasis-averse HCC and metastasis-incline HCC...
November 10, 2017: Oncotarget
Ali Zamani, Huahao Fan, Guangxiang Luo
Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver. A more thorough understanding of HCC pathogenesis will provide novel targets for development of cancer drugs to effectively treat HCC. To further this goal, we carried out a proteomic profiling of HCC cell lines Huh-7.4 and Huh-7.5. These two cell lines were derived from subgenomic HCV RNA-replicating Huh-7 cells upon clearance of HCV RNA by antiviral drug treatment. Initially, the tumorigenicity of each cell line was determined and compared in parallel in the same immunedeficient mice...
November 10, 2017: Oncotarget
Xinglong Zheng, Wenyan Liu, Junxi Xiang, Peng Liu, Mengyun Ke, Bo Wang, Rongqian Wu, Yi Lv
Nonalcoholic fatty liver disease (NAFLD) has become a major risk factor for hepatocellular carcinoma (HCC) worldwide. However, the underlying mechanism remains insufficiently elucidated. The expression of Collagen I, an important component of extracellular matrix (ECM), was increased during the progression from simple steatosis to NASH. The purpose of this study was to investigate the role of Collagen I in NAFLD-related HCC. To study this, the decellularized liver matrix, which preserves the pathological changes of ECM, was prepared from the human fatty liver (FLM) and human normal liver (NLM)...
November 10, 2017: Oncotarget
Xiu-Yan Huang, Zi-Li Huang, Tao Niu, Zhen-Qian Wu, Bin Xu, Yong-Hua Xu, Xin-Yu Huang, Qi Zheng, Jian Zhou, Zi Chen, Zhao-You Tang
Background: Increasing amounts of evidence indicate that Missing in metastasis B (MIM-B) promotes cancer metastasis. Here, we sought to better understand the mechanism through which MIM-B promotes tumor metastasis in hepatocellular carcinoma (HCC). Methods: We performed confocal microscopy analysis to determine the distributions of MIM-B and caveolin-1 and conducted co-immunoprecipitation assays to detect the interactions between MIM-B and caveolin-1 in vitro. We performed transwell assays to analyze the invasive ability of HCC cells...
November 10, 2017: Oncotarget
Hong Zhang, Xiaoxing Li, Yang Yang, Yanjie Zhang, Hui-Yun Wang, X F Steven Zheng
Hepatocellular carcinoma (HCC) is a male-dominant cancer and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous anti-androgen and -AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR-dependent transcriptome, stimulates oncogenic growth and determines therapeutic response to enzalutamide, a second generation of AR antagonist...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Wen-Bin Liu, Wei-Dong Jia, Jin-Liang Ma, Ge-Liang Xu, Hang-Cheng Zhou, Yan Peng, Wei Wang
GTP-binding protein 4 (GTPBP4), as a novel member of GTPases involved in the synthesis of 60S subunit and maturation, is closely related to cell proliferation and growth. Till now, a small number of existing studies have found a contradictory dual role of GTPBP4 in cancer. Whether the expression level of GTPBP4 in hepatocellular carcinoma (HCC) is associated with the patients' prognosis or its function and underlying molecular mechanisms still remains unclear. In the present study, the above issues were explored for the first time...
November 7, 2017: Oncotarget
Wenfeng Zhang, Di Mu, Kai Feng
Hepatocellular carcinoma (HCC) is one of the most malignant tumors in Chinese people and offers poor prognosis. Tumor tissue, like normal tissue, is hierarchically differentiated. Thus, minor tumor cell populations able to differentiate, such as stem cells, sustain tumor self-renewal and proliferation. The fact that liver cancer stem cells (CSCs) with different surface markers appear heterogeneous with respect to oncogenesis and drug resistance indicates that subpopulations of surface markers preserve the hierarchical potential of differentiation during proliferation, deterioration and relapse...
October 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Xiacheng Sun, Haiyan Cao, Lei Zhan, Chun Yin, Gang Wang, Ping Liang, Jibin Li, Zhe Wang, Bingrong Liu, Qichao Huang, Jinliang Xing
BACKGROUND AND AIMS: Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumor cells remained largely unknown. METHODS: In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of HCC cells...
December 6, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
Shujiao He, Junyi Zhang, Wan Zhang, Fengsheng Chen, Rongcheng Luo
BACKGROUND: Forkhead box A1 (FOXA1) expression is associated with various types of tumors; however, the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure. METHODS: Here, we investigated the role of FOXA1 in the development of HCC by applying gene function gain and loss analysis to HepG2 and Hep3B cell lines, and comparing outcomes with those of clinical HCC samples. RESULTS: Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), which encodes protein PI3Kp85 (p85), was identified as a FOXA1 target gene...
December 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
Liang Liang, Li Gao, Xiao-Ping Zou, Meng-Lan Huang, Gang Chen, Jian-Jun Li, Xiao-Yong Cai
MicroRNA (miR)-338-5p has been studied in hepatocellular carcinoma (HCC); however, the diagnostic value and molecular mechanism underlying its actions remains to be elucidated. The present study aimed to validate the diagnostic ability of miR‑338‑5p and further explore the underlying molecular mechanism. Data from eligible studies, Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) datasets were gathered in the data mining and the integrated meta‑analysis, to evaluate the significance of miR‑338‑5p in diagnosing HCC comprehensively...
November 21, 2017: Molecular Medicine Reports
Shakir Saleem, Ruqaiyah Khan, Muhammad Afzal, Imran Kazmi
Hepatocellular carcinoma (HCC) is the fifth leading cause of death and is generally typified by elevated liver enzyme biomarkers, antioxidants, and chronic inflammation of hepatocytes. Although currently available drugs have shown remarkable alleviation of the cancerous condition, but at the same time they present a more severe challenge of toxic effects due to chemotherapy. Therefore, in order to bring more patient-compliant therapy, we aimed to refurbish the use of a COX inhibitor, oxyphenbutazone (OPB), with low dose of methotrexate (MTX) to treat diethyl nitrosamine (DENA)-induced HCC in Wistar rats and in Hep3B cells...
December 4, 2017: Molecular and Cellular Biochemistry
Jianting Long, Chunlin Jiang, Baoxian Liu, Qiangsheng Dai, Ruixi Hua, Cui Chen, Bing Zhang, Heping Li
The strength and duration of STAT3 signaling are tightly controlled by multiple negative feedback mechanisms under physical conditions. However, how these serial feedback loops are simultaneously disrupted in cancers, leading to constitutive activation of STAT3 signaling in hepatocellular carcinoma (HCC), remains obscure. Here we report that miR-589-5p is elevated in HCC tissues, which is caused by recurrent gains. Overexpression of miR-589-5p correlates with poor overall and relapse-free survival in HCC patients...
November 28, 2017: Cancer Letters
Syuan-Ling Lin, Sheng-Ming Wu, I-Hsiao Chung, Yang-Hsiang Lin, Ching-Ying Chen, Hsiang-Cheng Chi, Tzu-Kang Lin, Chau-Ting Yeh, Kwang-Huei Lin
Thyroid hormone, 3,3',5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation and cell proliferation, via binding to its nuclear thyroid receptors (TR). Previous microarray and Chromatin immunoprecipitation (ChIP)-on-ChIP analyses have revealed that interferon-stimulated gene 20 kDa (ISG20), an exoribonuclease involved in the antiviral function of interferon, is up-regulated by T3 in HepG2-TR cells. However, the underlying mechanisms of ISG20 action in tumor progression remain unknown to date...
November 28, 2017: Neoplasia: An International Journal for Oncology Research
Hongyan Xue, Guo-Yan Tian
Accumulating documents have revealed that microRNAs (miRNAs) play critical roles in the development and progression of tumors. MiR-429 has been reported to be involved in regulating various cellular processes. However, its biological role and underlying mechanism in hepatocellular carcinoma (HCC) still need to be further studied. The present study aimed to investigate the function of miR-429 in the progression of HCC. In terms of this paper, it was found that miR-429 was down-regulated in HCC tissues and cells...
November 27, 2017: Archives of Biochemistry and Biophysics
Guanyu Wang, Fulu Dong, Zhiyao Xu, Sherven Sharma, Xiaotong Hu, Dafang Chen, Lumin Zhang, Jinping Zhang, Qinghua Dong
BACKGROUND: MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC. METHODS: To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses...
December 1, 2017: BMC Cancer
Bo Ren, Hui Liu, Hang Gao, Shutong Liu, Zehui Zhang, Andrew M Fribley, Michael U Callaghan, Zhixiang Xu, Qinghua Zeng, Yulin Li
Hepatocellular carcinoma (HCC) is one of the most serious and deadly diseases worldwide with limited options for effective treatment. Biomarker-based active compound targeting therapy may shed some light on novel drugs for HCC. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) play important roles in the regulation of cell fate and have become novel signaling targets for the development of anticancer drugs. Celastrol, a triterpene from traditional Chinese medicine, has been reported to possess anti-tumor effects on various cancers...
November 3, 2017: Oncotarget
Nissar Wani, Bo Zhang, Kun-Yu Teng, Juan Barajas, Tasneem Motiwala, Peng Hu, Lianbo Yu, Rafael Brüschweiler, Kalpana Ghoshal, Samson T Jacob
Hepatocellular carcinoma (HCC) is the most prevalent and a highly aggressive liver malignancy with limited therapeutic options. Here, the therapeutic potential of zerumbone, a sesquiterpene derived from the ginger plant Zingiber zerumbet, against HCC was explored. Zerumbone inhibited proliferation and clonogenic survival of HCC cells in a dose-dependent manner by arresting cell at the G2/M phase, and inducing apoptosis. To elucidate the underlying molecular mechanism, a phosphokinase array was performed that showed significant inhibition of the PI3K/AKT/mTOR and STAT3 signaling pathways in zerumbone treated HCC cells...
November 29, 2017: Molecular Cancer Research: MCR
Aldona Kasprzak, Karol Rogacki, Agnieszka Adamek, Karolina Sterzyńska, Wiesława Przybyszewska, Agnieszka Seraszek-Jaros, Celina Helak-Łapaj, Przemysław Pyda
Introduction: The role of Wnt/ β -catenin signaling pathway in HCV-associated hepatocellular carcinogenesis is still unknown. Material and methods: This study aimed to perform quantitative analysis of immuno- and hybridocytochemical expression of β -catenin, E- and N-cadherins and HCV proteins (C, NS3, NS5A) in long-lasting (≥ 20 years) chronic hepatitis C (CH-C) (n = 54), hepatocellular carcinoma (HCC) (n = 61), and control liver samples (n = 8). Results: Typical membranous expression of β -catenin in the control liver was higher than in the CH-C and HCC (p = 0...
October 2017: Archives of Medical Science: AMS
Shuai Wang, Fa-Ji Yang, Xun Wang, Yuan Zhou, Bo Dai, Bing Han, Hu-Cheng Ma, Yi-Tao Ding, Xiao-Lei Shi
Poly (ADP-ribose) polymerase 1 (PARP-1) is a crucial contributor to exacerbate ischemia and reperfusion (IR) injury and cancer process. However, there is little research into whether PARP-1 affects the hepatocellular carcinoma (HCC) recurrence after liver transplantation. In this study, we investigated the influence of PARP-1 on hepatic neutrophil mobilizing and phenotype shifting which may lead to HCC recurrence after liver transplantation. We found that rats received the grafts with warm ischemic injury had higher risk of HCC recurrence, which was markedly prevented by pharmacological inhibition of PARP-1 after liver transplantation...
October 24, 2017: Oncotarget
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