MicroRNA-27b up-regulated by human papillomavirus 16 E7 promotes proliferation and suppresses apoptosis by targeting polo-like kinase2 in cervical cancer
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Fei Liu1,2,*, Shimeng Zhang1,3,*, Zhen Zhao4, Xinru Mao1, Jinlan Huang1, Zixian Wu1, Lei Zheng1, Qian Wang1
1Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
2Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, China
3Central Laboratory, Shenzhen Shekou People’s Hospital, Shenzhen 518000, China
4Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD 20892, USA
*These authors have contributed equally to this work
Qian Wang, e-mail: [email protected]
Lei Zheng, e-mail: [email protected]
Keywords: microRNA-27b, HPV16 E7, cervical cancer, polo-like kinase2, DGCR8
Received: June 24, 2015 Accepted: December 30, 2015 Published: February 20, 2016
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.
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