HRK是重要的凋亡调控基因，我们发现HRK启动子甲基化和转录因子调控紊乱导致其在肿瘤中表达沉默（已发表于Am J Pathol,2013,182:84-95),同时注意到它可能受长非编码RNA（lncRNA）调控。本课题在此基础上深入研究lncRNA调控HRK的机制。我们在前列腺癌中发现了一个新的lncRNA（命名为HDOT），它可能作为competing endogenous RNA（ceRNA）或通过enhancer-like功能在表观遗传水平、转录水平和转录后水平调控HRK的表达。研究内容包括①HDOT是否与组蛋白修饰因子和转录因子结合形成复合物，影响组蛋白修饰（甲基化、乙酰基化），从而促进HRK表达。②HDOT是否作为ceRNA竞争性结合对HRK有负调控作用的microRNA，阻断其对HRK的抑制作用。③HDOT-HRK调控紊乱在前列腺癌发生发展中的作用。

HRK is an important apoptotic regulator. We found HRK was silenced in tumors due to promoter methylation and transcription factor dysregulation (published in Am J Pathol,2013,182:84-95), and noted long noncoding RNA (lncRNA) might regulate HRK expression. In this project, we explore the mechanisms of HRK regulation by lncRNA. We have found a novel lncRNA HDOT which may regulate HRK expression at epigenetic, transcriptional and post-transcriptional levels, as a competing endogenous RNA or by enhancer-like function in prostate cancer. We will investigate ①whether HDOT forms complexes with histone modifiers and transcription factors, thus regulating histone modification (methylation and acetylation) and inducing HRK expression; ②whether HDOT functions as a ceRNA that binds with HRK-targeting microRNAs, attenuating the inhibition function of these microRNAs; ③the role of HDOT-HRK dysregulation in prostate cancer.