Browsing by Author "Hsia, Yu"

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Identification of the common regulators for hepatocellular carcinoma induced by hepatitis B virus X antigen in a mouse model
(2012-01-01)
Lu, Jeng-Wei
;
Hsia, Yu
;
Yang, Wan-Yu
;
Lin, Yu-I
;
Li, Chao-Chin
Hepatitis B virus X antigen plays an important role in the development of human hepatocellular carcinoma (HCC). The key regulators controlling the temporal downstream gene expression for HCC progression remains unknown. In this study, we took advantage of systems biology approach and analyzed the microarray data of the HBx transgenic mouse as a screening process to identify the differentially expressed genes and applied the software Pathway Studio to identify potential pathways and regulators involved in HCC. Using subnetwork enrichment analysis, we identified five common regulator genes: EDN1, BMP7, BMP4, SPIB and SRC. Upregulation of the common regulators was validated in the other independent HBx transgenic mouse lines. Furthermore, we verified the correlation of their RNA expression levels by using the human HCC samples, and their protein levels by using the human liver disease tissue arrays. EDN1, bone morphogenetic protein (BMP) 4 and BMP7 were upregulated in cirrhosis, BMP4, BMP7 and SRC were further upregulated in hepatocellular or cholangiocellular carcinoma samples. The trend of increasing expression of the common regulators correlates well with the progression of human liver cancer. Overexpression of the common regulators increases the cell viability, promotes migration and invasiveness and enhances the colony formation ability in Hep3B cells. Our approach allows us to identify the critical genes in hepatocarcinogenesis in an HBx-induced mouse model. The validation of the gene expressions in the liver cancer of human patients and their cellular function assays suggests that the identified common regulators may serve as useful molecular targets for the early-stage diagnosis or therapy for HCC.
Liver Development and Cancer Formation in Zebrafish
(2011-06-01)
Lu, Jeng-Wei
;
Hsia, Yu
;
Tu, Hsiao-Chen
;
Hsiao, Yung-Chun
;
Yang, Wan-Yu
Liver is the largest organ in the human body, and it regulates many physiological processes. Many studies on liver development in different model organisms have demonstrated that the mechanism of hepatogenesis is conserved in vertebrates. The identification of the genes and regulatory pathways involved in liver formation provides a basis for the diagnosis of liver diseases and therapeutic interventions. Hepatocellular carcinoma is the third leading cause of mortality worldwide. In the last decade, genetic alterations, which include the gain and loss of DNA, as well as mutations and epigenomic changes, have been identified as important factors in liver cancer. Many genetic pathways are dysregulated during carcinogenesis. Here, we review the gene regulatory networks that underlie liver organogenesis and the dysregulation of these pathways in liver cancer. The genes and pathways involved in hepatogenesis and liver cancer are largely conserved between zebrafish and humans, making this an ideal model organism for the study of this disease. A better understanding of liver development may aid in the development of new diagnostic and therapeutic approaches to liver cancer. Birth Defects Research (Part C) 93: 157-172, 2011. (C) 2011 Wiley-Liss, Inc.