Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition
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摘要Genomic amplification of regional chromosome 8q24 is a common event in human cancers. In hepatocellular carcinoma (HCC), a highly aggressive malignancy that is rapidly fatal, recurrent 8q24 gains can be detected in >50% of cases. In this study, attempts to resolve the 8q24 region by way of array comparative genomic hybridization for affected genes in HCC revealed distinctive gains of block of proliferation 1 (BOP1). Gene expression evaluation in an independent cohort of primary HCC (n = 65) revealed frequent BOP1 up-regulation in tumors compared with adjacent nontumoral liver (84.6%; P < 0.0001). Significant associations could also be drawn between increased expressions of BOP1 and advance HCC staging (P = 0.004), microvascular invasion (P = 0.006), and shorter disease-free survival of patients (P = 0.02). Examination of expression of C-MYC, a well-known oncogene located in proximity to BOP1, in the same series of primary HCC cases did not suggest strong clinicopathologic associations. Functional investigations by small interfering RNA-mediated suppression of BOP1 in HCC cell lines indicated significant inhibition on cell invasion (P < 0.005) and migration (P < 0.05). Overexpression of BOP1 in the immortalized hepatocyte cell line L02 showed increase cellular invasiveness and cell migratory rate (P < 0.0001). In both gene knockdown and ectopic expression assays, BOP1 did not exert an effect on cell viability and proliferation. Evident regression of the epithelial-mesenchymal transition (EMT) phenotype was readily identified in BOP1 knockdown cells, whereas up-regulation of epithelial markers (E-cadherin, cytokeratin 18, and γ-catenin) and down-regulation of mesenchymal markers (fibronectin and vimentin) were seen. A corresponding augmentation of EMT was indicated from the ectopic expression of BOP1 in L02. In addition, BOP1 could stimulate actin stress fiber assembly and RhoA activation. Conclusion: Our findings underline an important role for BOP1 in HCC invasiveness and metastasis potentials through inducing EMT and promoting actin cytoskeleton remodeling. © 2011 American Association for the Study of Liver Diseases.
著者Chung K.-Y., Cheng I.K.-C., Ching A.K.-K., Chu J.-H., Lai P.B.-S., Wong N.
期刊名稱Hepatology
出版年份2011
月份7
日期1
卷號54
期次1
出版社John Wiley & Sons Inc.
出版地United States
頁次307 - 318
國際標準期刊號0270-9139
電子國際標準期刊號1527-3350
語言英式英語

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