title: miR-34a and its novel target, NLRC5, are associated with HPV16 persistence.
abstract: Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5.
authors.affiliation: Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin 150081, Heilongjiang, PR China.
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gynaecology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, PR China.
authors.forename: Libo
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin 150081, Heilongjiang, PR China.
authors.forename: Zhenji
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang, PR China.
authors.forename: Yushu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynaecology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, PR China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, ,The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, Heilongjiang, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin 150081, Heilongjiang, PR China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin 150081, Heilongjiang, PR China.
authors.forename: Fangjia
authors.initials: F
authors.lastname: Tong
authors.affiliation: Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin 150081, Heilongjiang, PR China.
authors.forename: Huihuang
authors.initials: H
authors.lastname: Lou
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin 150081, Heilongjiang, PR China. Electronic address: weilanlan_1119@163.com.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wei
mesh_terms: D000328:Adult; D002460:Cell Line; D002584:Cervix Uteri / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C548042:NLRC5 protein, human
keywords: Cervical cancer; Human papillomavirus type 16, persistent infection; NLRC5; miR-34a; p65