Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Up-regulated gene 4 (URG4), stimulated by HBxAg, is a novel gene located on chromosome 7 (7p13). The full-length URG4 clone is 3.607 kb and encodes a polypeptide of 922 amino acids, with a molecular weight of 104 kDa (GeneID: 55665). It promotes cell growth, growth factor-independent survival, and anchorage-independent growth in HepG2 cells, and it accelerates tumor formation in nude mice. Hence, URG4 may be a natural effector of HBxAg and a putative oncogene that contributes to multi-step hepatocarcinogenesis. Cyclin D1 is frequently over-expressed in hepatocellular carcinoma, exhibiting a number of malignant phenotypes. We found that down-regulation of URG4 through RNA interference-mediated silencing suppressed cell proliferation in HepG2 cells. Over-expression of URG4 up-regulated cyclin D1 mRNA expression, whereas RNA interference-mediated URG4 silencing diminished cyclin D1 mRNA expression in HepG2 cells. The data suggest that URG4 may play an important role in the development of hepatocellular carcinoma by partially regulating the expression of cyclin D1 and has potential for use as a therapeutic target for hepatocellular carcinoma.
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PMID:RNA interference-mediated URG4 gene silencing diminishes cyclin D1 mRNA expression in HepG2 cells. 2071 98

Evidence indicated that the x gene of human HBV can cause cancer in transgenic mice, moreover, HBxAg was so far the most frequent and strong antigen among those HBV markers expressed in hepatocellular carcinoma (HCC) tissues. Aiming to enhance killing of HCC by effector cells, we established an anti-HBx/anti-CD3 hybrid-hybridomas by fusion of anti-HBx hybridoma cells with FITC-labeled anti-CD3 HAT sensitive cells, and followed by FACStar sterile cell sorting, HAT selection and eventually verified by ELISA and double bridging assay. Using two color cytometric analysis, we found that bispecific monoclonal antibody (BsAb) remarkably enhanced in vitro effector-target cell conjugates (48.3% vs. 8.5%). In in vivo study, BsAb retargeting effector cells were significantly more effective than that of effector cells alone in shrinkage of LTNM4 HCC xenografts (HBxAg positive) in nude mice, not only in fresh inoculated tumors but also in established tumors (p<0.01, p<0.01, respectively). Besides, pronounced apoptotic cell death and infiltration of lymphocytes in the peripheral of tumor nodules can also be witnessed in the tissues treated by BsAb plus effector cells, but not in the controls. The results demonstrated that antiHBx/anti-CD3 BsAb was able to redirect effector cells for lysis of HBxAg positive HCC cells both in vitro and in vivo and it also indicated that shrinkage of tumors in nude mice with therapy of BsAb retargeting effector cells was partially due to initiation of apoptotic cell death.
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PMID:Preparation and application of anti-HBx/anti-CD3 bispecific monoclonal antibody (BsAb) retargeting effector cells for lysis of human hepatoma xenografts in nude mice. 2159 26

Hepatocellular carcinoma (HCC) originates from liver cells and is one of the most common malignant cancers in the world. microRNAs (miRNA), are single strand non-coding RNA molecules with the length of 18-25 nucleotides. miRNAs play an important role in the development of HCC, i.e., miRNAs have a significant impact on multistep hepatocellular carcinogenesis including cellular migration and invasion. URG4/URGCP (up-regulated gene-4/upregulator of cell proliferation) is up-regulated in the presence of HBxAg and has been identified and characterized by Satiroglu-Tufan et al. The full-length URG4/URGCP is 3.607 kb. Overexpression of URG4/URGCP in the presence of HBV X protein may function as a putative oncogene that significantly contributes to multi-step hepatocarcinogenesis. In this study, we aimed to investigate potential miRNA expression changes in HepG2 cell line model system in the presence of URG4/URGCP and in the absence of URG4/URGCP, which was suppressed by RNA interference. To functionally characterize URG4/URGCP, independent cultures of HepG2 cells were stably transfected with pcDNA3 or pcDNA3-URG4/URGCP. Relative quantification of whole genome miRNAs was analyzed by RT-PCR using human whole genome miRNA qPCR profiling kits. Among the 1,034 human miRNAs investigated by the arrays, 77 miRNAs were up-regulated and nine miRNAs were down-regulated in the presence of URG4/URGCP. In conclusion, we have analyzed miRNA profiles in HepG2 cells in presence or absence of URG4/URGCP gene using RNA interference. Some of these miRNAs may play roles in URG4/URGCP gene related disease development through the regulation of different signaling pathways.
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PMID:Investigation of microRNA expression changes in HepG2 cell line in presence of URG4/URGCP and in absence of URG4/URGCP suppressed by RNA interference. 2305 99

Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative.
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PMID:HBV induced HCC: major risk factors from genetic to molecular level. 2399 21

Hepatitis B virus (HBV) infection is a global health problem that causes a wide range of pathological outcomes, including cirrhosis and hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) stress induction by HBV infection has been implicated in liver carcinogenesis and disease progression with chronic inflammation via enhanced inflammation, oxidative stress-mediated DNA damage, and hepatocyte proliferation. In the natural course of HBV infection, the accumulation of naturally occurring mutations in the HBV genome can generate several mutant types of HBV-encoded proteins, including three different proteins in the S ORF (SHBs, MHBs, and LHBs) and HBcAg in the C ORF, which could contribute to enhanced ER stress in infected hepatocytes mainly via increased ER accumulation of mutant proteins. However, it seems that there may be distinct capacity and pathway in ER stress-induction and distinct resulting clinical outcomes between HBV variants. In addition, the role of HBxAg mutations in ER stress remains unknown. However, it has been reported that HBxAg itself could exert ER stress in infected cells, resulting in HCC generation in chronic HBV patients. To date, review papers regarding ER stress-mediated HBV mutation have been limited into a specific mutation type: preS2 deletion. So, in this review, we will discuss details about various mutation types in all four regions of the HBV genome (preS1, preS2, S, and C) related to ER stress and their distinct ER stress mechanisms and clinical outcomes in terms of mutation types.
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PMID:Naturally Occurring Hepatitis B Virus Mutations Leading to Endoplasmic Reticulum Stress and Their Contribution to the Progression of Hepatocellular Carcinoma. 3070 71


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