高危人乳头瘤病毒E6、E7在细胞恶性转化中极为关键。近年来，长链非编码RNA在宫颈癌中的作用逐渐为人关注，但lncRNA与E6、E7的关系却鲜有报道。鉴于宫颈癌中E6、E7与miRNA的相互作用已有较多证据，我们大胆地猜想E6、E7通过调控lncRNA的表达，以竞争性内源RNA的机制影响宫颈癌的进展。为此，本课题拟在前期完成的HPV16阳性宫颈癌组织lncRNA表达谱基础上，采用芯片技术比较E6/E7沉默前后Caski细胞lncRNA表达谱的改变，从细胞水平鉴定受E6或E7调控的lncRNA。通过体内外实验观察其异常表达对宫颈癌肿瘤生物学效应的影响，结合双荧光素酶报告实验、免疫共沉淀、RNA pull-down等确定竞争结合的miRNA及下游靶基因。旨在进一步完善HPV致癌的分子机制，为从lncRNA、miRNA和HPV感染层面揭示宫颈癌的发病机理，探寻宫颈癌防治新策略提供科学依据。

High-risk human papillomaviruses (HR-HPVs) infection is considered the causative agents of cervical cancer and HPV genotypes 16 and 18 cause the majority of these cancers. It is well established that oncoproteins E6 and E7 are the major transforming agents, leading to carcinogenesis. Recently, some studies are carried out on long non-coding RNAs (lncRNAs) in cervical cancer with encouraging results. But there is scarcity of literature about the association of lncRNAs in HPV positive cervical cancer and their possible interactions. Considering that E6 and E7 have definite interactions with microRNAs (miRNAs) which can modulate the process of carcinogenesis, we hypothesized that HR-HPV infection may be a key factor inducing lncRNAs expression in cervical cancer, and some lncRNAs regulated by E6 or E7 can function as competing endogenous RNA (ceRNA) by competitively binding common miRNAs in cervical cancer development. .To test this hypothesis, we aim to identify lncRNAs regulated by HPV16 E6/E7 (named E6/E7 lncRNA) using microarray technology, and validate the relationship between E6/E7 lncRNAs and HPV16 E6/E7 expression. Further studies will be performed to clarify the biological functions of E6/E7 lncRNAs in cell proliferation, cell cycle, apoptosis, migration and invasion in vivo and in vitro through gain-of-function/loss-of-fuction experiments. Using dual-luciferase reporter assay, Ago2 immunoprecipitation and RNA pull-down, we will confirm the specific association between miRNA and E6/E7 lncRNA. In addition, we plan to examine the expression of E6/E7, lncRNA, miRNA and its target genes in sufficient series of well-defined clinical cervical tissues, tissue microarrays and different cervical cell lines by performing qRT-PCR, in situ hybridization (ISH) and immunohistochemical staining, and analyze the correlations between their expression and poor prognostic clinicopathologic parameters. Taken together, our study on HPV16 E6/E7 and host lncRNA-miRNA interactions will continue shedding more light on our understanding of the of the pathogenesis of cervcial tumorigenesis, and implicate its potential application for predicting prognosis or cancer therapy in the future.