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.
Lin LinQingqing CaiXiaoyan ZhangHongwei ZhangYang ZhongCongjian XuYanyun Li
