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HCC signaling pathway

Veerabrahma Pratap Seshachalam, Karthik Sekar, Kam M Hui
BACKGROUND AND AIM: Hepatitis B virus, hepatitis C virus, alcoholic consumption and non-alcoholic fatty liver are the major known risk factors for Hepatocellular carcinoma (HCC). There have been very few studies comparing the underlying biological mechanisms associated with the different etiologies of HCC. In this study, we hypothesized the existence of different regulatory networks associated with different liver disease etiologies involved in hepatocarcinogenesis. METHODS: Using upstream regulatory analysis tool in ingenuity pathway analysis software, URs were predicted using differential expressed genes for HCC to facilitate the interrogation of global gene regulation...
April 19, 2018: Journal of Gastroenterology and Hepatology
Tong Zhang, Wei Liu, Wei Meng, Hui Zhao, Qing Yang, Shi-Jie Gu, Cui-Cui Xiao, Chang-Chang Jia, Bin-Sheng Fu
Introduction: Hepatocellular carcinoma (HCC) accounts for more than 90% of primary liver cancer. Although great progress has been made on HCC molecular mechanism and therapy techniques, the prognosis of HCC patient is poor due to high metastasis and recurrence. Materials and methods: Expression of miR-542-3p was quantified by quantitative real-time PCR (qRT-PCR). The role of miR-542-3p in HCC metastasis was examined using transwell and 3D-culture assay. qRT-PCR, Western blotting and luciferase reporter assay were used to elucidate the mechanisms of miR-542-3p-mediated cancer metastasis...
2018: OncoTargets and Therapy
Chaoxing Li, Li Liu, Valentin Dinu
Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway's topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs...
2018: PeerJ
Demin Jiao, Jun Chen, Yu Li, Xiali Tang, Jian Wang, Wei Xu, Jia Song, You Li, Huimin Tao, Qingyong Chen
Hepatocyte growth factor (HGF) overexpression is an important mechanism in acquired epidermal growth factor receptor (EGFR) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR-1-3p and miR-206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR-1-3p and miR-206 can overcome HGF-induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR-1-3p and miR-206 restored the sensitivities of lung cancer cells PC-9 and HCC-827 to gefitinib in present of HGF...
April 17, 2018: Journal of Cellular and Molecular Medicine
Derek J Erstad, Bryan C Fuchs, Kenneth K Tanabe
Molecular characterization of hepatocellular carcinoma (HCC) has greatly improved our understanding of disease pathogenesis. Mutational analysis, RNA and microRNA expression profiling, and epigenetic characterization have revealed common aberrations in oncogenes and tumor suppressors that correlate with disease biology and serve as a guide for the rational design of targeted therapies. These approaches have also led to the discovery of novel targets, including mutations in isocitrate dehydrogenase and chromatin remodeling enzymes...
April 17, 2018: Cancer
Jingcheng Wang, Yang Tian, Hui Chen, Hui Li, Shusen Zheng
The purpose of the present study was to investigate the underlying molecular mechanism of hepatocellular carcinoma (HCC) using bioinformatics approaches. The microarray dataset GSE64041 was downloaded from the Gene Expression Omnibus database, which included 60 tumor liver samples and 60 matched control samples. Differentially expressed genes (DEGs) between HCC and control groups were identified. Then functional enrichment analyses, protein‑protein interaction (PPI) network, sub‑network and integrated transcription factor (TF)‑microRNA (miRNA)‑target network analyses were performed for these DEGs...
April 12, 2018: Molecular Medicine Reports
Jianing Yan, Shibo Ying, Xiujun Cai
High-mobility group box 1 (HMGB1) is a potential therapeutic target and novel biomarker in a variety of malignant tumors, including hepatocellular carcinoma (HCC). More recently, a number of microRNAs (miRNAs) are identified as a class of regulators for broad control of HMGB1-mediated biological actions in eukaryotic cells. In this review article we will describe representative miRNAs involved in regulating the HMGB1 signaling pathways in HCC cell lines and/or animal models. We also propose the possible mechanisms underlying the miRNA/HMGB1 axis and discuss the future clinical significance of miRNAs targeting HMGB1 molecule for HCC therapy...
2018: BioMed Research International
Ashok K Singh, Archana S Bhadauria, Umesh Kumar, Vinit Raj, Amit Rai, Pranesh Kumar, Amit K Keshari, Dinesh Kumar, Biswanath Maity, Sneha Nath, Anand Prakash, Sudipta Saha
Inspired by the well-documented tumor protecting ability of paullones, recently, we synthesized novel paullone-like scaffolds, indole-fused benzo-oxazepines (IFBOs), and screened them against hepatocellular carcinoma (HCC) specific Hep-G2 cells. Three of the synthesized compounds significantly attenuated the progression of HCC in vitro. By computational studies, we further discovered that IFBOs exhibited a stable binding complex with the IL-6 receptor. In this context, we investigated in vivo study using the nitrosodiethyl amine (NDEA)-induced HCC model, which strengthened our previous findings by showing the blockade of the IL-6 mediated JAK2/STAT3 oncogenic signaling pathway...
April 12, 2018: Scientific Reports
Chuan Yan, Qiqi Yang, Zhiyuan Gong
Hepatocellular carcinoma (HCC) is one of the most common cancers and it usually develops from a background of liver fibrosis or inflammation. The crosstalk between tumor cells and stromal cells plays an important and stimulating role during tumor progression. Previously we found in a krasV12 -induced zebrafish HCC model that oncogenic hepatocytes activate hepatic stellate cells (HSCs) by up-regulation of serotonin and activate neutrophils and macrophages by up-regulation of cortisol. In the present study, we found a novel signaling transduction mechanism between oncogenic hepatocytes and HSCs...
April 9, 2018: Neoplasia: An International Journal for Oncology Research
Jinbiao Chen, Yanfei Qi, Yang Zhao, Dominik Kaczorowski, Timothy A Couttas, Paul R Coleman, Anthony S Don, Patrick Bertolino, Jennifer R Gamble, Mathew A Vadas, Pu Xia, Geoffrey W McCaughan
Primary liver cancer is the 3rd leading cause of cancer deaths worldwide with very few effective treatments. Sphingosine kinase 1 (SphK1), a key regulator of sphingolipid metabolites, is over-expressed in human hepatocellular carcinoma (HCC) and our previous studies have shown that SphK1 is important in liver injury. We aimed to explore the role of SphK1 specifically in liver tumorigenesis using the SphK1 knockout ( SphK1 -/- ) mouse. SphK1 deletion significantly reduced the number and the size of DEN-induced liver cancers in mice...
March 20, 2018: Oncotarget
Guangshan Yang, Gaofei Fan, Tengyue Zhang, Kelong Ma, Jin Huang, Miao Liu, Xiaolu Teng, Kun Xu, Pingsheng Fan, Dongmiao Cheng
BACKGROUND The aim of this study was to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in the reversal effect of verapamil (VER) on chemo-resistance to Adriamycin (ADM) in treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS HCC cell lines SMMC-7721 and BEL-7402 were used as model cell lines. High-throughput transcriptome sequencing based on Illumina technology was used to screen whether UCHL1 mediated the reversal effect of VER on chemo-resistance. Quantitative real-time PCR (qRT-PCR) was performed to determine the expression level of UCHL1 mRNA in HCC cells, and western blot analysis was performed to examine the protein expression of UCHL1 protein in HCC cells...
April 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Weidong Jiang, Dacheng Wen, Lulu Gong, Yu Wang, Zefeng Liu, Fangying Yin
The importance of circular RNAs (circRNAs) in human cancers has gradually been acknowledged. In hepatocellular carcinoma (HCC), several circRNAs have been reported to regulate tumor growth and metastasis. However, the role of hsa_circ_0000673 in HCC remains largely unknown. In this study, we found that hsa_circ_0000673 was significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Moreover, we found that hsa_circ_0000673 knockdown markedly inhibited the proliferation and invasion of HCC cells in vitro...
April 6, 2018: Biochemical and Biophysical Research Communications
Chakrabhavi Dhananjaya Mohan, Nirvanappa C Anilkumar, Shobith Rangappa, Muthu K Shanmugam, Srishti Mishra, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Atanu Bhattacharjee, Gautam Sethi, Alan Prem Kumar, Basappa, Kanchugarakoppal S Rangappa
Aberrant activation of NF-κB is linked with the progression of human malignancies including hepatocellular carcinoma (HCC), and blockade of NF-κB signaling could be a potential target in the treatment of several cancers. Therefore, designing of novel small molecule inhibitors that target NF-κB activation is of prime importance in the treatment of several cancers. In the present work, we report the synthesis of series of 1,3,4-oxadiazoles, investigated their anticancer potential against HCC cells, and identified 2-(3-chlorobenzo[b]thiophen-2-yl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole (CMO) as the lead compound...
2018: Frontiers in Oncology
Wenpeng Liu, Lei Kang, Juqiang Han, Yadong Wang, Chuan Shen, Zhifeng Yan, Yanhong Tai, Caiyan Zhao
Background: Insulin-like growth factor-1 receptor (IGF-1R) is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC). Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Materials and methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay...
2018: OncoTargets and Therapy
Meng-Lan Wang, Dong-Bo Wu, Ya-Chao Tao, Lan-Lan Chen, Cui-Ping Liu, En-Qiang Chen, Hong Tang
BACKGROUND: It has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant. RESULTS: As compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg...
April 2, 2018: Virology Journal
Hai Jiang, Zhenyu Zhou, Shaowen Jin, Kang Xu, Heyun Zhang, Junyang Xu, Qing Sun, Jie Wang, Junyao Xu
Protein arginine methyltransferases (PRMTs) catalyse protein arginine methylation and play an important role in many biological processes. Aberrant PRMT expression in tumour cells has been documented in several common cancer types; however, its precise contribution to hepatocellular carcinoma (HCC) cell invasion and metastasis is not fully understood. In this study, we identified a new oncogene, PRMT9, whose overexpression strongly promotes HCC invasion and metastasis. PRMT9 expression was detected more frequently in HCC tissues than in adjacent noncancerous tissues...
March 30, 2018: Cancer Science
Jai-Jen Tsai, Fei-Ting Hsu, Po-Jung Pan, Chia-Wen Chen, Yu-Cheng Kuo
BACKGROUND/AIM: In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo. MATERIALS AND METHODS: HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively...
April 2018: Anticancer Research
Yisong Xu, Cheng Zhang, Hui Liang, Shanshuang Hu, Pengkun Li, Linna Liu, Xianglong Duan, Chao Chen, Yani Zhang, Penggao Dai
Acquired resistance to 5-fluorouracil (5-FU) frequently occurs in patients with hepatocellular carcinoma (HCC), the underlying molecular mechanisms of which are poorly understood. The aim of this study was to identify candidate genes and associated signalling pathways that may play a role in developing drug resistance following repeated 5-FU treatments. In this work, we established 5-FU-resistant cells (HepG2/5-FU) using stepwise increasing concentrations of 5-FU in parental HepG2 cells. Using transcriptome sequencing, we found that the expressions of the Wnt signalling genes, including negative regulators (DKK1, DKK3, ZNRF3, RNF43 and APC2) and positive regulators (FZD10 and DVL1), were significantly downregulated and upregulated in HepG2/5-FU cells, respectively, resulting in increased Wnt signalling...
March 27, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Tatsuhiro Shibata, Yasuhito Arai, Yasushi Totoki
Hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) are more frequent in East Asia including Japan. Compiling 1,340 multi-ethnic HCC genomes, the largest cohort ever reported, identified comprehensive landscape of HCC driver genes, which constitutes three core drivers (TP53, TERT and WNT signaling) and combination of infrequent alterations in various cancer pathways. By contrast, five core driver genes (TP53, ARID1A, KRAS, SMAD4 and BAP1) with characteristic molecular alterations including fusion transcripts involving FGFR2 and the PKA pathway, and IDH1/2 mutation constituted the BTC genomes...
March 23, 2018: Cancer Science
Lin Wang, Chen Chen, Shuzhi Feng, Jianli Tian
Rapid proliferation and migration are the main features of hepatocellular carcinoma (HCC) cells, which serve an essential role in carcinogenesis and are a hallmark of cancer therapy resistance. Previous studies have reported that tumor necrosis factor‑α‑induced protein‑8 like‑2 (TIPE‑2) is involved in cancer initiation and the progression of HCC. The present study aimed to clarify the role of TIPE‑2 in HCC carcinogenesis, growth and aggressiveness. The effects of TIPE‑2 on HCC were determined using colony forming and cell cycle analyses...
March 20, 2018: Molecular Medicine Reports
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