Abstract 3960: MicroRNA-23b targeting urokinase-type plasminogen activator facilitates human papillomavirus type 16 E6 induction of cervical cancer cell migration

Abstract

Abstract Aberrant expression of microRNA in human cervical cancer is associated frequently with human papillomavirus (HPV) integration. MicroRNA-23b (miR-23b) is often down-regulated in HPV-associated cervical cancer. Also, urokinase-type plasminogen activator (uPA), a target of miR-23b, is reported to be over-expressed in cervical cancer. Thus, in the present study, the functional role of miR-23b in HPV-16 E6 associated cervical cancer development was investigated. Knockdown of oncoprotein E6 by E6 siRNA in HPV-16 positive human cervical carcinoma SiHa cells and CaSki cells led to an increase in the expression of miR-23b and a decrease in the expression of uPA as assessed by quantitative RT-PCR and Western blot analyses. Besides, uPA is confirmed to be the target of miR-23b as transient transfection of SiHa cells with miR-23b precursor vector repressed uPA expression and also the activity of luciferase reporter carrying the 3’UTR of uPA mRNA. uPA is known to be involved in cell migration and cell invasion. By wound healing assay, the cell migration rate of SiHa cells was reduced upon E6 as well as uPA knockdown. Moreover, the effect of E6 siRNA on cell migration was offset upon transfection with anti-miR-23b inhibitor. The results indicate that HPV-16 E6 may regulate cell migration through miR-23b/uPA pathway. Furthermore, p53 is a well-known gene target of HPV-16 E6. Knockdown of p53 by p53 siRNA decreased the miR-23b expression and increased the uPA expression. This shows that p53 may mediate the E6 effect on miR-23b/uPA expressions and thus cell migration of human cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3960. doi:10.1158/1538-7445.AM2011-3960