title: MiR-122 directly inhibits human papillomavirus E6 gene and enhances interferon signaling through blocking suppressor of cytokine signaling 1 in SiHa cells.
abstract: Human Papillomavirus (HPV) 16 infection is considered as one of the significant causes of human cervical cancer. The expression of the viral oncogenes like E6 and E7 play an important role in the development of the cancer. MiR-122 has been reported to exhibit a strong relationship with hepatitis viruses and take part in several tumor development, while the effects of miR-122 on HPV infection and the HPV viral oncogenes expression still remain unexplored. In this study, using RNAhybrid software, the potential binding sites between miR-122 and HPV16 E6 and E7 mRNAs were identified. Over and loss of miR-122 function showed that miR-122 could directly bind with HPV16 E6 mRNA and significantly inhibit its expression in SiHa cells, which was further confirmed by constructing the miR-122-E6-mu to eliminate the miR-122 binding effects with E6. The increase of the expression of type I interferon (IFN) and its classical effective molecules and the phosphorylation of signal transducers and activators of transcription (STAT1) protein indicated that miR-122 might enhance type I interferon in cervical carcinoma cells, which explained the significant reduction of HPV16 E7 and E6*I mRNA expression. This might be due to the binding between miR-122 and suppressor of cytokine signaling 1 (SOCS1) mRNA, which is the suppressor of interferon signaling pathway. Moreover, it was identified that the miR-122 binding position was nt359-nt375 in SOCS1 mRNA. Taken together, this study indicated that HPV16 could be effectively inhibited by miR-122 through both direct binding with E6 mRNA and promoting SOCS1-dependent IFN signaling pathway. Thus, miR-122 may serve as a new therapeutic option for inhibiting HPV infection.
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China; IBP-UC Group for Immunotherapy, CAS Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Junming
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Li
authors.affiliation: The Heilongjiang Key Laboratory of Immunity and Infection, Harbin, Heilongjiang, China.
authors.forename: Qingmeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China; The Heilongjiang Key Laboratory of Immunity and Infection, Harbin, Heilongjiang, China.
authors.forename: Wuqi
authors.initials: W
authors.lastname: Song
authors.affiliation: The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Instructions, Harbin, Heilongjiang, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Instructions, Harbin, Heilongjiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: The Heilongjiang Key Laboratory of Immunity and Infection, Harbin, Heilongjiang, China.
authors.forename: Aixia
authors.initials: A
authors.lastname: Zhai
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jinyun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Shang
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China; The Heilongjiang Key Laboratory of Immunity and Infection, Harbin, Heilongjiang, China; The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Instructions, Harbin, Heilongjiang, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China; The Heilongjiang Key Laboratory of Immunity and Infection, Harbin, Heilongjiang, China; The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Instructions, Harbin, Heilongjiang, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors* / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors*; D002583:Uterine Cervical Neoplasms / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D007370:Interferon Type I; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C059731:oncogene protein E7, Human papillomavirus type 16