title: Interferon-β induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells.
abstract: Infection by human papillomavirus (HPV) can cause cervical intraepithelial neoplasia (CIN) and cancer. Down-regulation of E6 and E7 expression may be responsible for the positive clinical outcomes observed with IFN treatment, but the molecular basis has not been well determined. As miRNAs play an important role in HPV induced cervical carcinogenesis, we hypothesize that IFN-β can regulate the expressions of specific miRNAs in cervical cancer cells, and that these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic potential. In this study, we found that miR-129-5p to be a candidate IFN-β inducible miRNA. MiR-129-5p levels gradually decrease with the development of cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela cells. This study is the first report of a cellular miRNA with anti-HPV activity and provides new insights into regulatory mechanisms between the HPV and the IFN system in host cells at the miRNA level.
authors.affiliation: Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jiarong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shuangdi
authors.initials: S
authors.lastname: Li
authors.affiliation: Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yixia
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wan
mesh_terms: D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000821:virology
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D009856:Oncogene Proteins, Viral; D016329:Sp1 Transcription Factor; D016899:Interferon-beta