Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis

Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, PR, China.
Cancer biology & therapy (Impact Factor: 3.07). 06/2007; 6(5):668-74. DOI: 10.4161/cbt.6.5.3955
Source: PubMed

ABSTRACT The molecular mechanisms underlying hepatitis B virus encoded HBx protein-mediated tumorigenesis are not fully understood. In order to gain a better view of the effects of HBx on transcriptional regulation and hepatocarcinogenesis, the expression profiles of liver and tumor tissues from 6- and 18-month-old p21-HBx transgenic and control mice were monitored using oligo microarrays. Data analysis demonstrated that 42 genes were deregulated in both 6- and 18-month-old HBx transgenic mouse tissues. Gene ontology assisted analysis classified these genes into functionally related clusters that encode proteins related to metabolism, signal transduction, transcription regulation and stress responses. Among them, cytoskeletal genes, including microtubule genes tubulinbeta2 (Tubb2), tubulinbeta3 (Tubb3) and tubulinbeta6 (Tubb6), intermediate filament genes periplakin, keratin 8 (K8) and keratin 18 (K18) and actingamma1 (Actg1), were closely clustered and upregulated in liver tissues. These results were validated by semi-quantitative RT-PCR in both mouse and human HCC tissues. The upregulation of K8 and K18 was only detected in p21-HBx but not p21-HBsAg liver tissues, suggesting that the global change in the expression of cellular cytoskeletal genes was correlated with the expression of HBx transgene. These findings propose for the first time that systemic dysregulation of cellular cytoskeletal genes is involved in HBx-induced hepatocarcinogenesis.

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    • "Other protein targets for HBx are damaged DNA binding proteins, p53, proteasome subunits; these proteins interacts with the cyclic AMP-responsive element, ATF-2 and basal transcription factors [69]. It has been found that during HBx-induced-HCC many cellular cytoskeletal genes such as microtubule genes tubulinb 2, tubulinb 3, tubulinb 6, keratin 8 (K-8) and keratin 18 (K-18), acting1 (Actg1) and intermediate filament genes periplakin were dysregulated, As it has been documented that these genes were closely clustered and up regulated in liver tissues [70]. The metastasis-associated protein 1 (MTA1) gene is one of the important transcriptional target of HBx protein; It has been found that MTA1 activates hypoxia-inducible factor 1α and vascular endothelial growth factor which contributes to angiogenesis in hepatic cancer [71]. "
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative.
    BioMed Research International 08/2013; 2013:810461. DOI:10.1155/2013/810461 · 3.17 Impact Factor
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    • "Immunoblotting were carried out mainly as described (44) using antibodies against Smad4 (provided by Dr Ye-Guang Chen), Smad2/3 (#3102, Cell Signal Technology, Inc.), eIF5 (sc-282, Santa Cruz Biotechnology, Inc.), MEF2 (sc-313, Santa Cruz Biotechnology), Myogenin (QC1653, Yuanpinghao Biotechnology, Beijing, China), caveolin3 (ab2912, Abcam plc, Cambridge, UK) and α-actin (BM0001, Boster Biological Technology, Wuhan, China). Immunostaining was carried out mainly as described (45). "
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    ABSTRACT: MicroRNAs (miRNAs) have recently been proposed as a versatile class of molecules involved in regulation of a variety of biological processes. However, the role of miRNAs in TGF-β-regulated biological processes is poorly addressed. In this study, we found that miR-24 was upregulated during myoblast differentiation and could be inhibited by TGF-β1. Using both a reporter assay and Northern blot analysis, we showed that TGF-β1 repressed miR-24 transcription which was dependent on the presence of Smad3 and a Smads binding site in the promoter region of miR-24. TGF-β1 was unable to inhibit miR-24 expression in Smad3-deficient myoblasts, which exhibited accelerated myogenesis. Knockdown of miR-24 led to reduced expression of myogenic differentiation markers in C2C12 cells, while ectopic expression of miR-24 enhanced differentiation, and partially rescued inhibited myogenesis by TGF-β1. This is the first study demonstrating a critical role for miRNAs in modulating TGF-β-dependent inhibition of myogenesis, and provides a novel mechanism of the genetic regulation of TGF-β signaling during skeletal muscle differentiation.
    Nucleic Acids Research 02/2008; 36(8). DOI:10.1093/nar/gkn032 · 9.11 Impact Factor
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    ABSTRACT: Objective The aim of this study was to use lung cancer targeting binding polypeptide ZS-9 to screen cDNA library of human lung cancer and obtain ZS-9 specific ligand to confirm tumor marker of non small-cell lung cancer. Methods Artificially synthesize biotin labeled peptide ZS-9, anchored ZS-9 in the enzyme label plate coupled by avidin, used ZS-9 as probe to screen cDNA library of human lung cancer, after screening, obtained bacteriophage clone specifically binding with anchored polypeptide ZS-9. Extracted plasmid of bacteriophage and performed sequencing after amplified by PCR. Results It was demonstrated by bioinformatic analysis on the sequence of ligand binded by lung cancer specific peptide ZS-9 that the ligand was the cytoskeletal protein periplakin on the surface of lung cancer cells, suggesting that periplakin might be a new marker for non-small-cell lung cancer in lung cancer. Conclusion Use specific lung cancer binding peptide to screen new tumor marker periplakin in lung cancer and further studies on its biologic functions in genesis and development of lung cancer are still needed.
    The Chinese-German Journal of Clinical Oncology 07/2013; 12(7). DOI:10.1007/s10330-013-1178-y
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