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Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway

Oncogene volume 30, pages 2401–2410 (2011)Cite this article

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Abstract

Deregulation of microRNA (miRNA or miR) expression in human cervical cancer is associated frequently with human papillomavirus (HPV) integration. miR-23b is often downregulated in HPV-associated cervical cancer. Interestingly, urokinase-type plasminogen activator (uPA), the miR-23b target, is detected in cervical cancer, but not in normal cervical tissues. Thus, the importance of miR-23b and uPA in HPV-associated cervical cancer development is investigated. In this study, the high-risk subtype HPV-16 E6 oncoprotein was found to decrease the expression of miR-23b, increase the expression of uPA, and thus induce the migration of human cervical carcinoma SiHa and CaSki cells. uPA is the target gene for miR-23b as the miR repressed uPA expression and interacted with the 3′-untranslated region of uPA mRNA. The tumor suppressor p53 is known to be inactivated by HPV-16 E6. A consensus p53 binding site is detected in the promoter region of miR-23b, whereas p53 trans-activated and also interacted with the miR’s promoter. Therefore, p53 is believed to mediate the HPV-16 E6 downregulation of miR-23b. From the above, miR-23b/uPA are confirmed to be involved in HPV-16 E6-associated cervical cancer development.

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Acknowledgements

The study is supported by grants from Hong Kong Research Grants and Council Earmarked Grants 466908, 467609.

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  1. School of Biomedical Sciences, Faculty of Medicine, Science Centre, The Chinese University of Hong Kong, Hong Kong SAR, China

    C L Au Yeung, T Y Tsang, P L Yau & T T Kwok

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  1. C L Au Yeung
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  2. T Y Tsang
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Correspondence to T T Kwok.

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Au Yeung, C., Tsang, T., Yau, P. et al. Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway. Oncogene 30, 2401–2410 (2011). https://doi.org/10.1038/onc.2010.613

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