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Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes
  • 分类:Q343[生物学—遗传学] Q343.1[生物学—遗传学]
  • 作者机构:[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
  • 相关基金: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).
中文摘要:

人的乳头状瘤病毒(HPV ) 包括高风险(HR ) 并且低风险(LR ) 子类型在遗传型和显型上有可区分的变化。多重 HR-HPVs 的合作感染,由 HPV16 出发了,在在女性的颈的癌症是普通的。最近积累的报告集中了于在病毒和主人之间的相互作用,特别地在由指向病毒的染色体的抗病毒的防卫的人的 microRNAs (miRNAs ) 的角色。这里,我们在大多数 HR-HPVs,不是 LR-HPVs 的染色体发现了 miRNAs 的一个保存得好的目标地点,由扫描风险的不含糊的子类型的 24 HPV 上的人的 miRNAs 的所有潜在的目标地点。这个地点被二不太普通的人的 miRNAs, miR-875 和 miR-3144 指向,并且位于 E6 oncogene 开的读框架(ORF ) 和有第一种选择的重叠拼接病毒的早抄本的 exon。在确认测试, miR-875 和 miR-3144 被识别显著地压制目标记者活动并且禁止两综合地外长的 E6 和内长的 E6 oncogene 的表示。二 miRNAs 的高水平能禁止房间生长并且在 HPV16 积极的颈的癌症房间支持 apoptosis。这研究为大多数 HR-HPVs 提供 miRNAs 的一个有希望的普通目标并且在瘤抑制上加亮二低表示人的 miRNAs 的效果。

英文摘要:

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.

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