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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/6041
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| Title: | Identification of the common regulators for hepatocellular carcinoma induced by hepatitis B virus X antigen in a mouse model |
| Authors: | Lu, JW;Yu, S;Yang, WY;Lin, YI;Li, CC;Tsai, TF;Chang, KW;Shieh, GS;Tsai, SF;Wang, HD;Yuh, CH |
| Contributors: | Institute of Molecular and Genomic Medicine |
| Abstract: | 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 sub-network enrichment analysis, we identified five common regulator genes: EDN1, BMP7, BMP4, SPIB and SRC. Up-regulation 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, BMP4 and BMP7 were up-regulated in cirrhosis, BMP4, BMP7, and SRC were further up-regulated 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. |
| Date: | 2012-01 |
| Relation: | Carcinogenesis. 2012 Jan;33(1):209-219. |
| Link to: | http://dx.doi.org/10.1093/carcin/bgr224 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0143-3334&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000298659200028 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84855395049 |
| Appears in Collections: | [蔡世峯] 期刊論文
[喻秋華] 期刊論文
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Size | Format | |
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| PUB22021908.pdf | | 15976Kb | Adobe PDF | 750 | View/Open |
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