title: Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV-related target genes for miR-29.
abstract: miRNAs have the potential to act on diverse downstream genes, and miRNA signatures of HPV-infected tissues may provide insight into HPV-related carcinogenesis. We set out to profile miRNA expression in HPV-infected samples and relate this to histological and grade-specific alterations in the spectrum of cervical carcinogenesis in vivo. A total of 31 miRNAs showed significant and continuous expression along with the progression from normal cervical tissue to cancer, and six of them were validated in 133 samples. By bioinformatics analyses, we established a putative HPV-associated miRNA-mRNA regulatory network, showing that miR-29 is the most highly enriched. We also found that YY1 and CDK6 were both positively correlated with E6/E7 RNA expression and targeted by tumour-suppressive miR-29. Evidence of miR-29 involvement in HPV infection was further verified in patient samples and by various experimental approaches. Taken together, our results suggest that HPVs have oncogenic properties at least in part by reshaping the milieu of cellular miRNAs. miR-29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR-29 in HPV-infected cells might be regulated in an indirect way.
authors.affiliation: Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Fenfen
authors.initials: F
authors.lastname: Wang
authors.forename: Junfen
authors.initials: J
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Shen
authors.forename: Jiansong
authors.initials: J
authors.lastname: Zhou
authors.forename: Weiguo
authors.initials: W
authors.lastname: Lu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wan
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D018390:Gene Targeting; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications* / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D050986:YY1 Transcription Factor / Q000378:metabolism
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6