Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis
Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis
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DOI：
10.4161/cbt.6.5.3955
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发表时间：
2007-05
影响因子：
3.6
通讯作者：
Qiang Sun;Youliang Wang;Ying'ai Zhang;Fang Liu;Xuan Cheng;N. Hou;Xiaohang Zhao;X. Yang
中科院分区：
文献类型：
--
作者：
Qiang Sun;Youliang Wang;Ying'ai Zhang;Fang Liu;Xuan Cheng;N. Hou;Xiaohang Zhao;X. Yang
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 de-regulated 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 tubulin-β2 (Tubb2), tubulin-β3 (Tubb3) and tubulin-β6 (Tubb6) , intermediate filament genes periplakin, keratin 8 (K8) and keratin 18 (K18) and actin-γ1 (Actg1) , were closely clustered and up-regulated in liver tissues. These results were validated by semi-quantitative RT-PCR in both mouse and human HCC tissues. The up-regulation 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.
