前列腺癌由雄激素依赖性演进为非依赖性的转型过程是前列腺癌治疗和研究的难点，lncRNA是否参与这一过程尚未见报道，我们以雄激素依赖的前列腺癌细胞株LNCaP和非依赖的LNCaP-AI为对象，利用芯片比较二者的lncRNA表达谱，发现大量差异表达的lncRNA,并初步发现lincRNA-ETS1-2对癌基因ETS-1有正调控作用，而lincRNA-ETS1-2在LNCaP-AI中表达上调，与IL-6/JAK/STAT3信号通路的激活相关。本项目将在此基础上进行以下研究：①在细胞水平研究lincRNA-ETS1-2受IL-6/JAK/STAT3通路转录激活，并上调ETS-1促进前列腺癌转型的机制；②利用小鼠移植瘤模型研究lincRNA-ETS1-2上调ETS-1促进前列腺癌侵袭转移的机制；③收集临床标本验证lincRNA-ETS1-2和ETS-1上调的相关性。为控制前列腺癌的转型提供理论依据。

The evolution from androgen-dependent prostate cancer to androgen-independent prostate cancer is a key problem for treatment and study of prostate cancer. Whether lncRNA is involved in this process has not been reported. Using microarray to compare the expression files of lncRNA between the androgen-dependent prostate cancer cell LNCaP and androgen-independent LNCaP-AI, a large number of differentially expressed lncRNAs were find out. The preliminary study results displayed that lincRNA-ETS1-2 had a positive-regulation effect on oncogene ETS-1, while the up-regulation of lincRNA-ETS1-2 in LNCaP-AI was associated with the activation of IL-6/JAK/STAT3 signaling pathway. On this basis, our group will explore the mechanism of lincRNA-ETS1-2 up-regulating the expression of oncogene ETS-1 to promote the evolution of androgen-independent prostate cancer, and how the lincRNA-ETS1-2 is activated transcriptionally by IL-6/JAK/STAT3 pathway at the cellular level. Moreover, mouse xenograft model will be constructed to observe that the up-regulation of ETS-1 by lincRNA-ETS1-2 result in raised activity in invasion and metastasis of prostate cancer. Last, clinical specimens of prostate cancer will also be collected to validate the correlation between lincRNA-ETS1-2 and ETS-1 up-regulation. This project can help to unravel the molecular mechanism of the transformation from androgen-dependent prostate cancer to androgen-independent prostate cancer, and provide a theoretical basis for the diagnostic and treatment of the androgen-independent prostate cancer.