title: 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.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Department of Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Central Laboratory, Shenzhen Shekou People's Hospital, Shenzhen 518000, China.
authors.forename: Shimeng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD 20892, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zixian
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: C474043:DGCR8 protein, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D050725:Papillomavirus E7 Proteins; D016601:RNA-Binding Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: DGCR8; HPV16 E7; cervical cancer; microRNA-27b; polo-like kinase2