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

For isolation of novel cellular transforming genes that potentially participated in hepatocarcinogenesis, we conducted anchorage-independent growth (AIG) assays on 10 human liver cancer cell lines and observed strong AIG capabilities in PLC5 and Huh7 but negligible in Tong cells. After cloning of genes by differential subtractive chain reactions (DSC) from strong AIG to AIG negative cells, we sequenced 2304 clones and identified 245 genes. After four stringent criteria for selection of transforming genes among DSC clones, our results of quantitative RT-PCR analysis indicated that six genes, DDX3, EIF3S2, CLIC1, HDGF, GPC3, and HSPCA were overexpressed in 64%, 62%, 60%, 58%, 49%, and 47%, respectively, of 45 hepatocellular carcinoma (HCC) tissues. The results of cellular transformation capability by AIG assays indicated that the transfectants of EIF3S2 showed the strongest (> 100-fold), DDX3 and CLIC1 were moderate, GPC3 and HSPCA were weak, and HDGF was none in forming colonies in soft agar. Together, our results suggested that Tong is a suitable human cell line for screening of overexpressed and/or cellular transforming genes. In addition, our results suggested that diverse functions of cellular transforming genes in various biological pathways could transform human Tong cells and potentially reveal new targets for drug development of HCC.
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PMID:Diverse cellular transformation capability of overexpressed genes in human hepatocellular carcinoma. 1498 4

Systematic proteomic studying of the mechanism of hepatocellular carcinoma (HCC) metastasis remains challenging. We performed comparative proteomic and pathway analysis of four human metastatic HCC cell lines to identify metastasis-associated proteins. These HCC cell lines had a similar genetic background but with an increasing potential of metastasis. Using a combination of two dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry, a total of 125 proteins and their post-translational modification forms or isoforms were found to be differentially expressed in the cell lines. Among them, 29 were gradually up-regulated whereas 17 were down-regulated with increasing metastatic potential. Instead of a traditional single-gene readout, global bioinformatics analysis was carried out, which revealed that the glycolysis pathway was the most significantly enriched pathway. The heat shock proteins (HSPs) centered and NF-kappaB centered networks were also enriched in the result, which may imply the key function of inflaming on metastasis. Meanwhile, knockdown of HDGF, an up-regulated protein and a target of NF-kappaB, induced cell apoptosis in the metastatic HCC cells. This work provides a demonstration that a combination of bioinformatics and comparative proteomics can help in finding out potential biomarkers associated with HCC metastasis on the level of pathways.
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PMID:Systematic proteomic analysis of human hepotacellular carcinoma cells reveals molecular pathways and networks involved in metastasis. 2146 25

Background and aim. Acetylsalicylic acid (ASA) has been shown to downregulate HCV expression; however, the involved mechanisms are unknown. We used proteomic analysis to compare protein expression profiles between human hepatocarcinoma cells (Huh7) and Huh7-HCV cells harboring expression of non-structural HCV proteins, to elucidate the mechanism(s) involved in ASA-mediated downregulation of HCV replication. Material and methods. Both cell lines were treated or untreated with 4 mM ASA and harvested at 0, 24, 48 and 72 h to isolate total proteins, which were resolved by two-dimensional gel electrophoresis (2DE) to separate them by isoelectric point (pI), followed by fractionation by molecular weight (MW). Gels were scanned and analyzed with PD-Quest software V8.0.1, and proteins were elucidated by the specific pI and MW using TAGIDENT software. Statistics analysis included the t-test. esults and Discussion. Different protein patterns among hepatocytes expressing HCV-proteins in ASA treated and untreated cells were found. Among proteins differentially expressed in Huh7-HCV cells, we found proteins related to cell proliferation (MTMR6, FAM22, HDGF and HCF-1) after 24 h of ASA treatment; and upregulation of angiostatin, PI4KA and STAT-1 after 48 h of treatment. Finally, at 72 h of ASA exposure, we identified overexpression of adenylsuccinate synthase, 2'-3'-di-deoxyadenosine, ubiquitin-protein-ligase E6A, adenylosuccinate-lyase and nibrin (NBN). Conclusion. We found that ASA induces different protein patterns in Huh7-HCV cells promoting activation of proteins involved in cell progression, repair of double strand breaks, proliferation, inhibition of apoptosis and growth stimulation at the same time that it decreased HCV expression.
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PMID:Use of proteomic analysis tools to identify HCV-proteins down-regulated by acetylsalicylic acid. 2401 90

The development of hepatocellular carcinoma (HCC) is an important complication of viral infection induced by hepatitis virus C, and our major research theme is to identify a new growth factor related to the progression of HCC. HDGF (hepatoma-derived growth factor) is a novel growth factor that belongs to a new gene family. HDGF was initially purified from the conditioned medium of a hepatoma cell line. HDGF promotes cellular proliferation as a DNA binding nuclear factor and a secreted protein acting via a receptor-mediated pathway. HDGF is a unique multi-functional protein that can function as a growth factor, angiogenic factor and anti-apoptotic factor and it participates in the development and progression of various malignant diseases. The expression level of HDGF may be an independent prognostic factor for predicting the disease-free and overall survival in patients with various malignancies, including HCC. Furthermore, the overexpression of HDGF promotes the proliferation of HCC cells, while a reduction in the HDGF expression inhibits the proliferation of HCC cells. This article provides an overview of the characteristics of HDGF and describes the potential role of HDGF as a growth-promoting factor for HCC.
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PMID:Hepatoma-Derived Growth Factor: Its Possible Involvement in the Progression of Hepatocellular Carcinoma. 2610 67

Hepatoma derived growth factor related protein-3 (HRP-3) is a HDGF growth factor family member that is expressed mainly in nervous tissues. It shares structural similarities with HDGF but differs in its expression and scope of action. It has recently attracted more attention due to its variable roles. HRP-3 was originally reported as a mitogenic factor. However, over the last decade, additional functions for this growth factor have been uncovered. In addition to its mitogenic activity, other physiological functions were discovered including those related to proliferation, differentiation, and maintenance of neurons, presenting it as a neurotrophic and neuroprotective growth factor. Interestingly, HRP-3 was also shown to be involved in the pathogenesis of certain tumors via its mitogenic, angiogenic, and antiapoptotic effects. Based on this, HRP-3 represents a molecule that can be targeted for the treatment of cancer and various neurodegenerative diseases.
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PMID:Insight into the roles of hepatoma derived growth factor related protein-3 under physiological and pathological conditions. 3007 99

microRNAs (miRNAs) regulate gene expression post-transcriptionally and have been extensively tested as therapeutic molecules against several human diseases. In vivo delivery of miRNAs needs to satisfy the following conditions: safety, efficiency, and long-term therapeutic effectiveness. To satisfy these conditions, we developed a tissue-adhesive nucleotide-polymer complex (NPX-glue) for in vivo delivery of miRNAs to treat hepatocellular carcinoma (HCC). Methods: Polyallylamine (PAA), a cationic polymer, was mixed with tumor-suppressing miR-141 to form NPX and then mixed with partially oxidized alginate (OA) to form NPX-glue. Delivery efficiency of miR-141:NPX-glue was determined in cultured HCC cells and in an implanted HCC tumor model. In vivo tumor-suppressive effects of miR-141 on HCC were examined in mice upon intratumoral injection of miR-141:NPX-glue. Result: NPX-glue was generated by mixing of NPX with OA, which eliminated the inherent cytotoxic effect of NPX. NPX-glue led to the efficient delivery of miR-141 and plasmid to cultured cells and solid tumors in mice, where their expression was maintained for up to 30 days. Upon intratumoral injection of miR-141:NPX-glue, the growth of the tumors was dramatically retarded in comparison with the negative control, NCmiR:NPX-glue, (p < 0.05). Molecular examination proved miR-141:NPX-glue efficiently regulated the target genes including MAP4K4, TM4SF1, KEAP1, HDGF, and TIAM1 and finally induced apoptosis of cancer tissues. Conclusion: Here, we show that NPX-glue delivers therapeutic miR-141 to solid tumors in a safe, stable, and long-term manner and prove that locoregional treatment of HCC is possible using the NPX-glue system.
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PMID:Tumor-suppressing miR-141 gene complex-loaded tissue-adhesive glue for the locoregional treatment of hepatocellular carcinoma. 3008 68

HDGF-related protein 3 (HRP3, also known as HDGFL3) belongs to the family of HDGF-related proteins (HRPs) and plays an essential role in hepatocellular carcinoma pathogenesis. All HRPs have a PWWP domain at the N-terminus that binds both histone and DNA substrates. Despite previous advances in PWWP domains, the molecular basis by which HRP3 interacts with chromatin is unclear. In this study, we solved the crystal structures of the HRP3 PWWP domain in complex with various double-stranded DNAs with/without bound histone peptides. We found that HRP3 PWWP bound to the phosphate backbone of the DNA minor groove and showed a preference for DNA molecules bearing a narrow minor groove width. In addition, HRP3 PWWP preferentially bound to histone peptides bearing the H3K36me3/2 modification. HRP3 PWWP uses two adjacent surfaces to bind both DNA and histone substrates simultaneously, enabling us to generate a model illustrating the recruitment of PWWP to H3K36me3-containing nucleosomes. Cell-based analysis indicated that both DNA and histone binding by the HRP3 PWWP domain is important for HRP3 recruitment to chromatin in vivo. Our work establishes that HRP3 PWWP is a new family of minor groove-specific DNA-binding proteins, which improves our understanding of HRP3 and other PWWP domain-containing proteins.
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PMID:The HRP3 PWWP domain recognizes the minor groove of double-stranded DNA and recruits HRP3 to chromatin. 3116 7