Utility of MicroRNAs and siRNAs in Cervical Carcinogenesis

Figure 1

Schematic model of the interaction between microRNAs and factors involved in malignant transformation caused by HPV E6 and E7 expression in cervical cancer cell. Cervical cancer is the second most common cause of cancer mortality in women worldwide and persistent infection with HPV is the main etiologic agent. HPV E6 and E7 deregulate cellular proliferation and inhibit the apoptotic mechanism by targeting p53 and pRb, respectively. In addition, E6 disrupts the expression of miR-23b, miR-218, and miR-34a via p53 degradation and their expression is transactivated by the binding of p53 to consensus sites in the promoter regions, affecting the expression of cell cycle regulators, such as E2, cyclin D1, CDK4, CDK6, E2F1, E2F3, E2F5, Bcl-2, SIRT1, p18, uPA, and LAMBD3. In the overexpression of miR-15/16 cluster by E7, E2F1 transactivates the c-Myb expression and represses the c-Myc expression, and then the microRNA cluster regulation is controlled by binding of c-Myc or c-Myb to promoter region of microRNA cluster. The increased expression of miR-15a/miR-16-1 induces the inhibition of cell proliferation, survival, and invasion. The downregulation of miR-203 by E7 is mediated by MAPK/PKC pathway.