Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes  

作　　者：Lin Lin Qingqing Cai Xiaoyan Zhang Hongwei Zhang Yang Zhong Congjian Xu Yanyun Li 

机构地区：[1]Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China [2]Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai 200032, China [3]Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China [4]Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China [5]School of Life Sciences and Technology, Tongji University, Shanghai 200092, China [6]Shanghai Center for Bioinformation Technology, Shanghai 200235, China [7]School of Life Sciences, Fudan University, Shanghai 200433, China

出　　处：《Protein & Cell》2015年第8期575-588,共14页蛋白质与细胞（英文版）

基　　金：We would like to extend our sincere gratitude to Dr. James Crabbe for his help in editing the manuscript. This work was supported by the National Natural Science Foundation of China （Grant No. 81101955）; and the Research Fund for the Doctoral Program of Higher Education of China （Grant No. 20110071120094）.

摘　　要：Human papillomaviruses （HPVs） including high.risk （HR） and low-risk （LR） subtypes have distinguishable variation on both genotypes and phenotypes. The co- infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accu- mulating reports have focused on the interaction be- tween virus and host, particularly the role of human microRNAs （miRNAs） in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miR- NAs, miR-875 and miR-3144, and is located in E6 onco- gene open reading frame （ORF） and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosisin HPV16-positive cervical cancer cells. This study pro- vides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low ex- pressed human miRNAs on tumour suppression.Human papillomaviruses （HPVs） including high.risk （HR） and low-risk （LR） subtypes have distinguishable variation on both genotypes and phenotypes. The co- infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accu- mulating reports have focused on the interaction be- tween virus and host, particularly the role of human microRNAs （miRNAs） in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miR- NAs, miR-875 and miR-3144, and is located in E6 onco- gene open reading frame （ORF） and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosisin HPV16-positive cervical cancer cells. This study pro- vides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low ex- pressed human miRNAs on tumour suppression.

关 键 词：human papillomavirus microRNA E6miR-875 miR-3144 

分 类 号：Q343[生物学—遗传学] Q343.1