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HCC signaling pathway

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https://www.readbyqxmd.com/read/28231410/transcriptomic-analyses-of-rna-binding-proteins-reveal-eif3c-promotes-cell-proliferation-in-hepatocellular-carcinoma
#1
Tangjian Li, Shengli Li, Di Chen, Bing Chen, Tao Yu, Fangyu Zhao, Qifeng Wang, Ming Yao, Shenglin Huang, Zhiao Chen, Xianghuo He
RNA-binding proteins (RBPs) play fundamental roles in the RNA life cycle. The aberrant expression of RBPs is often observed in human disease, including cancer. In this study, we screened for the expression levels of 1,542 human RBPs in The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA LIHC) samples and found 92 consistently up-regulated RBP genes in HCC compared with normal samples. Additionally, we performed a Kaplan-Meier analysis and found that high expression of 15 RBP genes was associated with poor prognosis in patients with HCC...
February 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28230855/simvastatin-induced-cell-cycle-arrest-through-inhibition-of-stat3-skp2-axis-and-activation-of-ampk-to-promote-p27-and-p21-accumulation-in-hepatocellular-carcinoma-cells
#2
Sin-Ting Wang, Hsiu J Ho, Jaw-Town Lin, Jeng-Jer Shieh, Chun-Ying Wu
Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and is one of the leading causes of cancer-related death worldwide. Simvastatin, an HMG-CoA reductase inhibitor, which decreases cholesterol synthesis by inhibiting mevalonate pathways and is widely used to treat cardiovascular diseases. Simvastatin exhibits anticancer effects against several malignancies. However, the molecular mechanisms underlying the anticancer effects of simvastatin on HCC are still not well understood. In this study, we demonstrated simvastatin-induced G0/G1 arrest by inducing p21 and p27 accumulation in HepG2 and Hep3B cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28211215/zkscan1-gene-and-its-related-circular-rna-circzkscan1-both-inhibit-hepatocellular-carcinoma-cell-growth-migration-and-invasion-but-through-different-signaling-pathways
#3
Zhicheng Yao, Jingyan Luo, Kunpeng Hu, Jizong Lin, He Huang, Qiangliang Wang, Peng Zhang, Zhiyong Xiong, Zejian Huang, Chonghua He, Bo Liu, Yang Yang
There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development, but the regulation and function of human circRNAs remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circZKSCAN1 was significantly lower (P<0.05) in the HCC samples compared with that in matched adjacent non-tumorous tissues by reverse transcription PCR (RT-PCR)...
February 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#4
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
: Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209511/heparanase-1-induced-shedding-of-heparan-sulfate-from-syndecan-1-in-hepatocarcinoma-cell-facilitates-lymphatic-endothelial-cell-proliferation-via-vegf-c-erk-pathway
#5
Shengjin Yu, Huiming Lv, He Zhang, Yu Jiang, Yu Hong, Rongjun Xia, Qifang Zhang, Weiwei Ju, Lili Jiang, Geng Ou, Jinhui Zhang, Shujing Wang, Jianing Zhang
Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface...
February 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28205209/characterization-of-the-gnmt-hecth9-prex2-tripartite-relationship-in-the-pathogenesis-of-hepatocellular-carcinoma
#6
Chung-Hsien Li, Chia-Hung Yen, Yen-Fu Chen, Kuo-Jui Lee, Cheng-Chieh Fang, Xian Zhang, Chih-Chung Lai, Shiu-Feng Huang, Hui-Kuan Lin, Yi-Ming Arthur Chen
The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N-methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9-mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28202495/expression-of-grk2-and-igf1r-in-hepatocellular-carcinoma-clinicopathological-and-prognostic-significance
#7
Song-Bai Lin, Li Zhou, Zhi-Yong Liang, Wei-Xun Zhou, Ye Jin
AIM: It has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC. METHODS: Expression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival...
February 15, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28195035/pre-s2-mutant-induced-mammalian-target-of-rapamycin-signal-pathways-as-potential-therapeutic-targets-for-hepatitis-b-virus-associated-hepatocellular-carcinoma
#8
Chiao-Fang Teng, Han-Chieh Wu, Woei-Cherng Shyu, Long-Bin Jeng, Ih-Jen Su
Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Pre-S2 mutant represents an HBV oncoprotein that is accumulated in the endoplasmic reticulum (ER) and manifests as type II ground glass hepatocytes (GGHs). Pre-S2 mutant can induce ER stress and initiate multiple ER stress-dependent or -independent cellular signal pathways, leading to growth advantage of type II GGH. Importantly, the mammalian target of rapamycin (mTOR) signal pathways are consistently activated throughout the liver tumorigenesis in pre-S2 mutant transgenic mice and in human HCC tissues, leading to hepatocyte proliferation, metabolic disorders, and HCC tumorigenesis...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28192402/loss-of-klf4-and-consequential-downregulation-of-smad7-exacerbate-oncogenic-tgf-%C3%AE-signaling-in-and-promote-progression-of-hepatocellular-carcinoma
#9
H Sun, Z Peng, H Tang, D Xie, Z Jia, L Zhong, S Zhao, Z Ma, Y Gao, L Zeng, R Luo, K Xie
Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28186991/c-terminal-truncated-hepatitis-b-virus-x-protein-regulates-tumorigenicity-self-renewal-and-drug-resistance-via-stat3-nanog-signaling-pathway
#10
Rachel Hiu Ha Ching, Karen Man Fong Sze, Eunice Yuen Ting Lau, Yung-Tuen Chiu, Joyce Man Fong Lee, Irene Oi Lin Ng, Terence Kin Wah Lee
Hepatitis B virus (HBV) is a major risk factor of chronic liver disease and hepatocellular carcinoma (HCC). Random integration of HBV DNA into the host genome is frequent in HCC leading to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). C-terminally truncated HBx (HBx-ΔC) has been implicated in playing a pro-oncogenic role in hepatocarcinogenesis. However, the mechanism whereby HBx-ΔC1 contributes to hepatocarcinogenesis remains unclear. In this study, we investigated the functional role of HBx-ΔC1 in regulating liver cancer stem cell (CSC) properties...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184024/oip5-a-target-of-mir-15b-5p-regulates-hepatocellular-carcinoma-growth-and-metastasis-through-the-akt-mtorc1-and-%C3%AE-catenin-signaling-pathways
#11
Hua Li, Jun Zhang, Mi-Jin Lee, Goung-Ran Yu, Xueji Han, Dae-Ghon Kim
Opa interacting protein 5 (OIP5) is upregulated in some types of human cancers, but the biological implications of its upregulation have not yet been clarified in human hepatocellular carcinoma (HCC). In this study, the signaling pathway downstream of OIP5 was analyzed by proteome kinase profiling. A putative microRNA targeting OIP5 was identified using a miRNA PCR array. Tumorigenicity and metastatic ability were examined in an orthotopic animal model. OIP5 expression was strongly detected in early and advanced tumors via gene expression profiling and immunohistochemical staining analyses...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28182015/mcm7-promotes-cancer-progression-through-cyclin-d1-dependent-signaling-and-serves-as-a-prognostic-marker-for-patients-with-hepatocellular-carcinoma
#12
Kai Qu, Zhixin Wang, Haining Fan, Juan Li, Jie Liu, Pingping Li, Zheyong Liang, Hongli An, Yina Jiang, Qiushi Lin, Xiaoqun Dong, Peijun Liu, Chang Liu
DNA replication is a central procedure of cell proliferation, whereas aberrant DNA replication is indicated to be a driving force of oncogenesis. Minichromosome maintenance complex component 7 (MCM7) plays an essential role in initiating DNA replication. To investigate the potential oncogenic properties and prognostic value of MCM7 in hepatocellular carcinoma (HCC), we conducted immunohistochemistry staining of MCM7 in 153 HCC samples and found that MCM7 high expression level was associated with worse overall survival (OS) of HCC patients...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28181235/new-advances-of-tmem88-in-cancer-initiation-and-progression-with-special-emphasis-on-wnt-signaling-pathway
#13
REVIEW
Yun-Xuan Ge, Chang-Hui Wang, Fu-Yong Hu, Lin-Xin Pan, Jie Min, Kai-Yuan Niu, Lei Zhang, Jun Li, Tao Xu
Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane. Recent studies showed that TMEM88 was involved in the regulation of several types of cancer. TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line. TMEM88 silencing in the ovarian cancer cell line CP70 resulted in significant upregulation of Wnt downstream genes (c-Myc, cyclin-D1) and other Wnt target genes including JUN, PTIX2, CTNNB1 (β-catenin), further supporting that TMEM88 inhibits canonical Wnt signaling pathway...
February 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28178673/actinidia-chinensis-planch-root-extract-inhibits-cholesterol-metabolism-in-hepatocellular-carcinoma-through-upregulation-of-pcsk9
#14
Mingyan He, Jiayun Hou, Lingyan Wang, Minghuan Zheng, Tingting Fang, Xiangdong Wang, Jinglin Xia
Actinidia chinensis Planch root extract (acRoots) is a traditional Chinese medicine with anti-tumor efficacy. To investigate the mechanisms responsible for this activity, we examined the effects of acRoots on cholesterol metabolism in hepatocellular carcinoma (HCC). mRNA chip analysis was used to identify the metabolic genes regulated by acRoots. The effects of acRoots on cholesterol synthesis and uptake were evaluated by measuring intracellular cholesterol levels and 3,3'-dioctadecylindocarbocyanine-labeled low-density lipoprotein (Dil-LDL) uptake...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177662/esculetin-induces-apoptosis-of-smmc-7721-cells-through-igf-1-pi3k-akt-mediated-mitochondrial-pathways
#15
Juan Li, Shuang Li, Xiuli Wang, Hongxin Wang
Esculetin (6,7-dihydroxycoumarin) is a coumarin derivative extracted from natural plants and has been reported to have anti-cancer activity. However, the mechanism by which esculetin prevents human hepatic cancer cell growth is still largely unknown. In this study, we investigated the effect of esculetin on human hepatocellular carcinoma (HCC) SMMC-7721 cells and explored the cell signal mechanism. Our data indicated that esculetin induced apoptosis in SMMC-7721 cells, which were supported by DAPI staining and Annexin V/PI staining...
February 3, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28177238/design-synthesis-and-biological-evaluation-of-mitochondria-targeted-flavone-naphthalimide-polyamine-conjugates-with-antimetastatic-activity
#16
Fujun Dai, Qian Li, Yuxia Wang, Chaochao Ge, Chenyang Feng, Songqiang Xie, Haoying He, Xiaojuan Xu, Chaojie Wang
Approximately 90% of cancer-associated deaths result from disseminated tumors, indicating the ineffectiveness of current therapies and the imperative need of antimetastatic drugs. A novel pharmacophore with flavonoid and naphthalimide moieties was constructed by using a fragment-based drug design and a series of eight flavone-naphthalimide-polyamine conjugates were synthesized. In vitro evaluation revealed that compound 6c with a homospermidine motif displayed better cell selectivity between cancerous and normal liver cells than amonafide did...
February 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28176469/epcam-liver-cancer-stem-like-cells-exhibiting-autocrine-wnt-signaling-potentially-originate-in-cirrhotic-patients
#17
Ritu Khosla, Archana Rastogi, Gayatri Ramakrishna, Viniyendra Pamecha, Ashok Mukhopadhyay, Madavan Vasudevan, Shiv Kumar Sarin, Nirupma Trehanpati
Hepatocellular carcinoma (HCC) is believed to originate from cancer stem cells (CSCs). While epithelial cell adhesion molecule (EpCAM) is a marker of normal hepatic stem cells (HSCs), EpCAM+ cells from HCC behave like CSCs. Since HCC mostly develops on a cirrhotic background, we sought to determine whether CSC-like EpCAM+ cells exist in patients with advanced cirrhosis. Both flow cytometry and immunohistochemistry showed that frequency of EpCAM+ cells in advanced cirrhosis was increased as compared to control...
February 8, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28167506/lipid-nanoparticle-mediated-delivery-of-anti-mir-17-family-oligonucleotide-suppresses-hepatocellular-carcinoma-growth
#18
Xinqiang Huang, Jill Magnus, Vivek Kaimal, Priya Karmali, Jian Li, Marlena Walls, Rene Prudente, Eric Sung, Mehran Sorourian, Robin Lee, Scott Davis, Xia Yang, Heather Estrella, Edmund C Lee, B Nelson Chau, Adam Pavlicek, Sonya Zabludoff
Hepatocellular carcinoma (HCC) is one of the most common human malignancies with poor prognosis and urgent unmet medical need. Aberrant expression of multiple members of the microRNA-17 (miR-17) family are frequently observed in HCC and their overexpression promotes tumorigenic properties of HCC cells. However, whether pharmacological inhibition of the miR-17 family inhibits HCC growth remains unknown. In the present study, we validated that the miR-17 family was up-regulated in a subset of HCC tumors and cell lines and its inhibition by a tough decoy inhibitor suppressed growth of Hep3B and HepG2 cells, which overexpress the miR-17 family...
February 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28164434/dual-inhibition-of-akt-and-c-met-as-a-second-line-therapy-following-acquired-resistance-to-sorafenib-in-hepatocellular-carcinoma-cells
#19
Peng Han, Hali Li, Xian Jiang, Bo Zhai, Gang Tan, Dali Zhao, Haiquan Qiao, Bing Liu, Hongchi Jiang, Xueying Sun
Sorafenib displays a limited efficacy for advanced hepatocellular carcinoma (HCC). Some HCC patients initially respond to sorafenib but eventually succumb to the disease, indicating that the acquired resistance to sorafenib reduces its beneficial effects. No alternative drugs are available after the failure of sorafenib therapy. Therefore, investigation of the mechanisms underlying the acquired resistance and development of second-line treatments for sorafenib-resistant HCC are urgently required. In the present study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways...
February 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28161506/mathematical-modelling-unveils-the-essential-role-of-cellular-phosphatases-in-the-inhibition-of-raf-mek-erk-signalling-by-sorafenib-in-hepatocellular-carcinoma-cells
#20
Zuzana Saidak, Anne-Sophie Giacobbi, Christophe Louandre, Chloé Sauzay, Youcef Mammeri, Antoine Galmiche
The RAS-RAF-MEK-ERK cascade is a key oncogenic signal transduction pathway activated in many types of tumours in humans. Sorafenib, the medical treatment of reference against advanced stages of hepatocellular carcinoma (HCC), inhibits the RAF-MEK-ERK cascade in HCC cells. Based on previous studies suggesting that this cascade is an important target of sorafenib in HCC cells, we explored its regulation using mathematical modelling and ordinary differential equations. We analysed the dynamic regulation of the core components of the RAF-MEK-ERK cascade in three human HCC cell lines (Huh7, Hep3B and PLC/PRF5) with heterogeneous responses to sorafenib...
February 2, 2017: Cancer Letters
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