TCGA whole-transcriptome sequencing data reveals significantly dysregulated genes and signaling pathways in hepatocellular carcinoma

This study systematically evaluates the TCGA whole-transcriptome sequencing data of hepatocellular carcinoma (HCC) by comparing the global gene expression profiles between tumors and their corresponding nontumorous liver tissue. Based on the differential gene expression analysis, we identified a number of novel dysregulated genes, in addition to those previously reported. Top-listing upregulated (CENPF and FOXM1) and downregulated (CLEC4G, CRHBP, and CLEC1B) genes were successfully validated using qPCR on our cohort of 65 pairs of human HCCs. Further examination for the mechanistic overview by subjecting significantly upregulated and downregulated genes to gene set enrichment analysis showed that different cellular pathways were involved. This study provides useful information on the transcriptomic landscape and molecular mechanism of hepatocarcinogenesis for development of new biomarkers and further in-depth characterization

Pim1 is upregulated by hypoxia in hepatocellular carcinoma and promotes tumor progression

Poster Session - Molecular pathogenesis, molecular pathology, cell biology and translational research: no. P-022INTRODUCTION: Hepatocellular carcinoma (HCC) is the second/third most common fatal cancer in Hong Kong and Southeast Asia associated with frequent tumor recurrence and metastasis. Apart from surgical intervention, tumor control at cellular and molecular levels can possibly improve clinical outcome. HCC is characteristically one of the most rapidly proliferating tumors which often outpace functional blood supply, leading to a regional oxygen deprivation. Therefore, molecular changes induced by hypoxia are attractive therapeutic targets. Overexpression of PIM1, a serine/threonine kinase, has been identified in recent years in solid cancers such as prostate cancer, gastric cancer, and pancreatic cancer. In the latter, PIM1 was upregulated by hypoxia. In this study, we aim at investigating the expression, functional role, and regulatory mechanism of PIM1 in HCC, which have …published_or_final_versio

Role of epac in the pathogenesis of ischemic stroke

Poster Presentations: Theme 2published_or_final_version15th Research Postgraduate Symposium, Hong Kong, China, 1-2 December 2010. In Abstract - Poste Presentations (Theme II) of 15th Research Postgraduate Symposium, 2010, p. 8

Sox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling

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Down-regulation of TIMP2 by HIF-1α/miR-210/HIF-3α regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma

Cancer metastasis is a multistep process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling, which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases (TIMP) 2 in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly down-regulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.8%; 23 of 55) in human HCCs and was significantly associated with liver invasion and poorer survival outcomes of HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Using an orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line, MHCC-97L, significantly reduced HCC progression as well as pulmonary metastasis. Mechanistically, TIMP2 suppression, in a hypoxic environment, was induced through a regulatory feedback circuit consisting of hypoxia-inducible factor (HIF) 1 alpha, microRNA-210 (miR-210), and HIF-3alpha. CONCLUSION: TIMP2 is frequently down-regulated in human HCCs and its down-regulation is associated with aggressive tumor behavior and poorer patient outcome. Its suppression is under the regulation of a novel feedback circuit consisting of HIF-1alpha/miR-210/HIF-3alpha. TIMP2 is an important regulator of ECM degradation and HCC metastasis. (Hepatology 2016;64:473-487).published_or_final_versio

PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma

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SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop

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The Impact Of Hypoxia In Hepatocellular Carcinoma Metastasis

Hypoxia is a common phenomenon in hepatocellular carcinoma (HCC). Hypoxia stabilizes transcription factor, hypoxia-inducible factor (HIF), to activate gene transcription. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF mediates expression of genes that are involved in every step of HCC metastasis including epithelial-mesenchymal transition, invasion of the extracellular matrix, intravasation, extravasation, and secondary growth of the metastases. Because HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. This review will summarize the current findings on the impact of hypoxia/HIF in HCC, with a particular focus on cancer metastasis