基于高通量测序数据的长非编码RNA调控网络及在癌症中的应用

Long non-coding RNA, a kind of RNA with regulation, have been paid a great attention recently. They can regulate numerous oncogenic and tumor-suppressor genes and play important roles in key cancer pathways. However, the analysis on their regulation is too one-sided, and lack of a comprehensive and systematic study. Moreover, it is difficult to understand their regulatory roles in cancer due to the lack of available data. Here, we combine high-throughput sequencing data from prostate cancer, liver cancer, pituitary tumor as well as their corresponding normal tissues (including polyA+ sequencing, polyA- sequencing and small RNA sequencing data) and public data, and by constructing multivariant co-expression network as background, to systematically study the long non-coding RNA regulatory network including in cis, in trans, ceRNA moles and transcription factor regulation. By combining the regulatory network with the data of three types of tumor, many cancer-related long non-coding RNAs and their functional modules as well as their regulatory molds are identified, which would be a pioneering work in characterizing cancer associated long non-coding RNAs and their regulatory roles and would provide a comprehensive and reliable resource for further experimental study.

长非编码RNA是近年来发现的一类数目众多且具有调控功能的分子，能够直接或间接调节众多原癌或抑癌基因的表达，其调控紊乱与癌症密切相关。然而，目前对其调控模式的研究大都过于片面，对其缺乏全面、系统地认识，且由于缺乏相关数据指导其在癌症中的调控方式研究困难较大。本项目借助前列腺癌、肝癌、脑垂体瘤及对应正常组织的高通量测序数据（包括polyA+测序、polyA-测序及小RNA测序数据）以及公共数据，针对长非编码RNA主要的调控模式，包括顺式调控、反式调控、竞争性调控模式以及转录因子对其进行的调控，以多元分子的共表达网络为背景，利用系统生物学的观点及方法构建长非编码RNA调控网络。我们通过将调控网络与三类肿瘤的数据相结合，对各肿瘤特异的及肿瘤间共同存在的以长非编码RNA为核心的关键调控模块进行系统分析，为深入理解长非编码RNA在肿瘤中的调控模式提供基础也为实验机制研究提供全面、可靠的资源。

长非编码RNA是近年来发现的一类数目众多且具有调控功能的分子，能够直接或间接调节众多原癌或抑癌基因的表达，其调控紊乱与癌症密切相关。然而，目前对其调控模式的研究大都过于片面，对其缺乏全面、系统地认识，且由于缺乏相关数据指导其在癌症中的调控方式研究困难较大。本项目借助前列腺癌、肝癌、脑垂体瘤及对应正常组织的高通量测序数据（包括polyA+测序、polyA-测序及小RNA测序数据）以及公共数据，针对长非编码RNA主要的调控模式，包括顺式调控、反式调控、竞争性调控模式以及转录因子对其进行的调控，以多元分子的共表达网络为背景，利用系统生物学的观点及方法构建长非编码RNA调控网络。我们通过将调控网络与三类肿瘤的数据相结合，对各肿瘤特异的及肿瘤间共同存在的以长非编码RNA为核心的关键调控模块进行系统分析，为深入理解长非编码RNA在肿瘤中的调控模式提供基础也为实验机制研究提供全面、可靠的资源。