MicroRNA-27b up-regulated by human papillomavirus 16 E7 promotes proliferation and suppresses apoptosis by targeting polo-like kinase2 in cervical cancer.

Abstract

The infection with high-risk human papillomavirus is linked to cervical cancer, nevertheless, the role of miRNAs regulated by HPV oncogenes in cancer progression remain largely unknown. Here, we knocked down endogenous E6/E7 in HPV16-positive CaSki cell lines, screened differences in miRNA expression profile with control using miRNA array. 38 miRNAs were down-regulated and 6 miRNAs were up-regulated in the E6/E7 silenced CaSki cells (>2-fold changes with P <0.05). The levels of miR-27b, miR-20a, miR-24, miR-93, and miR-106b were verified by qPCR in E6/E7 silenced CaSki and SiHa cells. MiR-27b, up-regulated by E7, promoted CaSki and SiHa cell proliferation and invasion, inhibit paclitaxel-induced apoptosis. Dual-luciferase experiment confirmed miR-27b down-regulated its target gene PLK2 through the "seed regions". The tumor suppressor PLK2 inhibited SiHa cell proliferation, reduced cell viability, and promoted paclitaxel/cisplatin -induced apoptosis. Furthermore, DGCR8 was found to mediate the up-regulation of miR-27b by HPV16 E7. Our study demonstrated that HPV16 E7 could increase DGCR8 to promote the generation of miR-27b, which accelerated cell proliferation and inhibited paclitaxel-induced cell apoptosis through down-regulating PLK2. These findings provide an insight into the interaction network of viral oncogene, miR-27b and PLK2, and support the potential strategies using antisense nucleic acid of miR-27b for therapy of cervical cancer in the future.

• Authors: Fei Liu, Shimeng Zhang, Zhen Zhao, Xinru Mao, Jinlan Huang, Zixian Wu, Lei Zheng, Qian Wang
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 15 Pg. 19666-79 (Apr 12 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26910911 (Publication Type: Journal Article)

Chemical References

• DGCR8 protein, human
• MIRN27 microRNA, human
• MicroRNAs
• Papillomavirus E7 Proteins
• RNA-Binding Proteins
• oncogene protein E7, Human papillomavirus type 16
• PLK2 protein, human
• Protein Serine-Threonine Kinases

Topics

• Apoptosis (genetics)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Female
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Host-Pathogen Interactions
• Human papillomavirus 16 (genetics, metabolism, physiology)
• Humans
• MicroRNAs (genetics)
• Papillomavirus E7 Proteins (genetics, metabolism)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• RNA Interference
• RNA-Binding Proteins (genetics, metabolism)
• Up-Regulation
• Uterine Cervical Neoplasms (genetics, pathology, virology)