title: Activation of miR-9 by human papillomavirus in cervical cancer.
abstract: Cervical cancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervical cancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervical cancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervical cancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervical cancer and other HPV-induced cancers.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Weijun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.affiliation: People's Hospital of Guangxi Province, Nanning, China. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Hu
authors.affiliation: Pre-clinic and Forensic Medical School, Sichuan University, Chengdu, China. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Schwarz
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Perry W
authors.initials: PW
authors.lastname: Grigsby
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000821:virology*; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C062495:oncogene protein E7, Human papillomavirus type 6