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  ✔本篇論文使用華聯產品:Human OneArray  
 Surgery. 2012, 152(4):704-11. doi: 10.1016/j.surg.2012.07.020.
 Restoration of E-cadherin expression in pancreatic ductal adenocarcinoma treated with microRNA-101 
 Aamer M. Qazi, Oksana Gruzdyn, Assaad Semaan, Shelly Seward, Sreedhar Chamala, Vasu Dhulipala, Seema Sethi, Rouba Ali-fehmi, Philip A. Philip, David L. Bouwman, Donald W. Weaver, Scott A. Gruber, Ramesh B. Batchu
  Abstract
To investigate the possibility of inhibiting the progression of pancreatic ductal adenocarcinoma (PDAC) by facilitating the expression of E-cadherin through the enforced expression of microRNA-101 (miR-101). In situ hybridization was conducted with archival tissue using a double digoxigenin-labeled probe. Chromatin immunoprecipitation (ChIP) assay was conducted with EZ-Magna ChIPTM A. Gene profile analysis, Western blot, and immunoprecipitation assays were performed using standard protocols. We found that decreased miR-101 expression observed in archival patient tissues was significantly associated with poor prognosis indicated by low-intensity staining in high-grade tumors. ChIP assays using anti-enhancer of zeste homolog 2 (EZH2) antibodies indicated not only the interaction of EZH2 to the CDH1 (E-cadherin) promoter, but also that this interaction was significantly diminished in cells transfected with pre-miR-101. We observed a global downregulation of trimethylated lysine 27 of H3 histone (H3K27me3) along with upregulation of the enzymes histone deacetylase -1 and -2 with the re-expression of miR-101. Further, we observed lesser levels of transcriptional factors that inhibit the CDH1 promoter with pre-miR-101 treatment. Western blot analysis confirmed the enhanced E-cadherin expression. PANC-1 cells transduced with pre-miR-101 displayed markedly attenuated growth in SCID mice. These results suggest the potential therapeutic use of miR-101-enforced expression for inhibition of PDAC.
   

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  ✔本篇論文使用華聯產品:Human OneArray  
 Oncoscience. doi:10.18632/oncoscience.285.
 In silico and experimental analyses predict the therapeutic value of an EZH2 inhibitor GSK343 against hepatocellular carcinoma through the induction of metallothionein genes
 
 
 
  Abstract
There are currently no effective molecular targeted therapies for hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27)-specific methyltransferase, has been emerged as novel anticancer target. Our previous study has demonstrated that GSK343, an S-adenosyl-L-methionine (SAM)-competitive inhibitor of EZH2, induces autophagy and enhances drug sensitivity in cancer cells including HCC. In this study, an in silico study was performed and found that EZH2 was overexpressed in cancerous tissues of HCC patients at both gene and protein levels. Microarray analysis and in vitro experiments indicated that the anti-HCC activity of GSK343 was associated with the induction of metallothionein (MT) genes. In addition, the negative association of EZH2 and MT1/MT2A genes in cancer cell lines and tissues was found in public gene expression database. Taken together, our findings suggest that EZH2 inhibitors could be a good therapeutic option for HCC, and induction of MT genes was associated with the anti-HCC activity of EZH2 inhibitors.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Scientific Reports . doi: 10.1038/srep19156.
 A novel cell-penetrating peptide suppresses breast tumorigenesis by inhibiting β-catenin/LEF-1 signaling
 
 
 
  Abstract
The inhibition of β-catenin/LEF-1 signaling is an emerging strategy in cancer therapy. However, clinical targeted treatment of the β-catenin/LEF-1 complex remains relatively ineffective. Therefore, development of specific molecular targets is a key approach for identifying new cancer therapeutics. Thus, we attempted to synthesize a peptide (TAT-NLS-BLBD-6) that could interfere with the interaction of β-catenin and LEF-1 at nuclei in human breast cancer cells. TAT-NLS-BLBD-6 directly interacted with β-catenin and inhibited breast cancer cell growth, invasion, migration, and colony formation as well as increased arrest of sub-G1 phase and apoptosis; it also suppressed breast tumor growth in nude mouse and zebrafish xenotransplantation models, showed no signs of toxicity, and did not affect body weight. Furthermore, the human global gene expression profiles and Ingenuity Pathway Analysis software showed that the TAT-NLS-BLBD-6 downstream target genes were associated with the HER-2 and IL-9 signaling pathways. TAT-NLS-BLBD-6 commonly down-regulated 27 candidate genes in MCF-7 and MDA-MB-231 cells, which are concurrent with Wnt downstream target genes in human breast cancer. Our study suggests that TAT-NLS-BLBD-6 is a promising drug candidate for the development of effective therapeutics specific for Wnt/β-catenin signaling inhibition.
   

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  ✔本篇論文使用華聯產品:Human OneArray  
 Bmc Cancer. DOI 10.1186/s12885-015-1671-5.
 Upregulation of MicroRNA-19b predicts good prognosis in patients with hepatocellular carcinoma presenting with vascular invasion or multifocal disease
 
 
 
  Abstract
Background After surgical resection of hepatocellular carcinoma (HCC), recurrence is common, especially in patients presenting with vascular invasion or multifocal disease after curative surgery. Consequently, we examined the expression pattern and prognostic value of miR-19b in samples from these patients. Methods We performed a miRNA microarray to detect differential expression of microRNAs (miRNAs) in 5 paired samples of HCC and non-tumoral adjacent liver tissue and a quantitative real-time polymerase chain reaction (PCR) analysis to validate the results in 81 paired samples of HCC and adjacent non-tumoral liver tissues. We examined the associations of miR-19b expression with clinicopathological parameters and survival. MiR-19b was knocked down in Hep3B and an mRNA microarray was performed to detect the affected genes. Results In both the miRNA microarray and real-time PCR, miR-19b was significantly overexpressed in the HCC tumor compared with adjacent non-tumor liver tissues (P < 0.001). The expression of miR-19b was significantly higher in patients who were disease-free 2 years after surgery (P < 0.001). High miR-19b expression levels were associated with higher α-fetoprotein levels (P = 0.017). In the log-rank test, high miR-19b was associated with better disease-free survival (median survival 37.107 vs. 11.357; P = 0.022). In Cox multivariate analysis, high miR-19b predicted better disease-free survival and overall survival (hazards ratio [HR] = 0.453, 95 % confidence interval [CI] = 0.245–0.845, P = 0.013; HR = 0.318, CI = 0.120–0.846, P = 0.022, respectively). N-myc downstream regulated 1 (NDRG1) was downregulated, while epithelial cell adhesion molecule (EPCAM), hypoxia-inducible factor 1-alpha (HIF1A), high-mobility group protein B2 (HMGB2), and mitogen activated protein kinase 14 (MAPK14) were upregulated when miR-19b was knocked down in Hep3B. Conclusions The overexpression of miR-19b was significantly correlated with better disease-free and overall survival in patients with HCC presenting with vascular invasion or multifocal disease after curative surgery. MiR-19b may influence the expression of NDRG1, EPCAM, HMGB2, HIF1A, and MAPK14.
   

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 Amino Acids. doi: 10.1007/s00726-015-1956-7. Epub 2015 Mar 24..
 Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular endothelial cells
 
 
 
  Abstract
Genetic or nutritional deficiencies in homocysteine (Hcy) metabolism lead to hyperhomocysteinemia (HHcy) and cause endothelial dysfunction, a hallmark of atherosclerosis. In addition to Hcy, related metabolites accumulate in HHcy but their role in endothelial dysfunction is unknown. Here, we examine how Hcy-thiolactone, N-Hcy-protein, and Hcy affect gene expression and molecular pathways in human umbilical vein endothelial cells. We used microarray technology, real-time quantitative polymerase chain reaction, and bioinformatic analysis with PANTHER, DAVID, and Ingenuity Pathway Analysis (IPA) resources. We identified 47, 113, and 30 mRNAs regulated by N-Hcy-protein, Hcy-thiolactone, and Hcy, respectively, and found that each metabolite induced a unique pattern of gene expression. Top molecular pathways affected by Hcy-thiolactone were chromatin organization, one-carbon metabolism, and lipid-related processes [−log(P value) = 20–31]. Top pathways affected by N-Hcy-protein and Hcy were blood coagulation, sulfur amino acid metabolism, and lipid metabolism [−log(P value)] = 4–11; also affected by Hcy-thiolactone, [−log(P value) = 8–14]. Top disease related to Hcy-thiolactone, N-Hcy-protein, and Hcy was ‘atherosclerosis, coronary heart disease’ [−log(P value) = 9–16]. Top-scored biological networks affected by Hcy-thiolactone (score = 34–40) were cardiovascular disease and function; those affected by N-Hcy-protein (score = 24–35) were ‘small molecule biochemistry, neurological disease,’ and ‘cardiovascular system development and function’; and those affected by Hcy (score = 25–37) were ‘amino acid metabolism, lipid metabolism,’ ‘cellular movement, and cardiovascular and nervous system development and function.’ These results indicate that each Hcy metabolite uniquely modulates gene expression in pathways important for vascular homeostasis and identify new genes and pathways that are linked to HHcy-induced endothelial dysfunction and vascular disease.