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Oncotarget. 2016 Apr 12;7(15):19666-79. doi: 10.18632/oncotarget.7531.

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

Author information

1
Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
2
Department of Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
3
Central Laboratory, Shenzhen Shekou People's Hospital, Shenzhen 518000, China.
4
Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD 20892, USA.

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.

KEYWORDS:

DGCR8; HPV16 E7; cervical cancer; microRNA-27b; polo-like kinase2

PMID:
26910911
PMCID:
PMC4991410
DOI:
10.18632/oncotarget.7531
[Indexed for MEDLINE]
Free PMC Article

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