title: HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells.
abstract: High-risk human papillomavirus (HPV) type 16, which is responsible for greater than 50% of cervical cancer cases, is the most prevalent and lethal HPV type. However, the molecular mechanisms of cervical carcinogenesis remain elusive, particularly the early steps of HPV infection that may transform normal cervical epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues, and these groups of microRNAs are further reduced in cervical carcinoma. Among these miRNAs, miR196a expression is the most reduced in HPV16-infected tissues. Interestingly, miR196a expression is low in HPV16-positive cervical cancer cell lines but high in HPV16-negative cervical cancer cell lines. Furthermore, we found that only HPV16 early gene E5 specifically down-regulated miRNA196a in the cervical cancer cell lines. In addition, HoxB8, a known miR196a target gene, is up-regulated in the HPV16 cervical carcinoma cell line but not in HPV18 cervical cancer cell lines. Various doses of miR196a affected cervical cancer cell proliferation and apoptosis. Altogether, these results suggested that HPV16 E5 specifically down-regulates miR196a upon infection of the human cervix and initiates the transformation of normal cervix cells to cervical carcinoma.
authors.affiliation: 1] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [2] Department of Gynecological Oncology, Tumor Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Chanzhen
authors.initials: C
authors.lastname: Liu
authors.affiliation: 1] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [2] College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Lin
authors.affiliation: Obstetrics and Gynecology Center, Tsinghua University Second Hospital, Beijing 100049, China.
authors.forename: Lianqin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Chen
authors.affiliation: Obstetrics and Gynecology Center, Tsinghua University Second Hospital, Beijing 100049, China.
authors.forename: Zeyi
authors.initials: Z
authors.lastname: Cao
authors.affiliation: 1] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [2] Obstetrics and Gynecology Center, Tsinghua University Second Hospital, Beijing 100049, China.
authors.forename: Huancong
authors.initials: H
authors.lastname: Zuo
authors.affiliation: 1] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China [2] Obstetrics and Gynecology Center, Beijing Henghe Hospital, Beijing 100005, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Kehkooi
authors.initials: K
authors.lastname: Kee
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology; D000086082:Viroporin Proteins
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; C490669:HOXB8 protein, human; C542543:MIRN196 microRNA, human; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins