长链非编码RNA-HOTAIR在前列腺癌恶性进展及肿瘤干细胞中的作用及机制研究

项目名称： 长链非编码RNA-HOTAIR在前列腺癌恶性进展及肿瘤干细胞中的作用及机制研究

项目编号： No.81502577

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 党强

作者单位： 南方医科大学

项目金额： 18万元

中文摘要： 前列腺癌已成为中国男性的常见及多发肿瘤，而且大多数病例发现时已为晚期，对于晚期肿瘤患者，去势治疗（ADT）仍然是目前的首选治疗方案，但或迟或早，肿瘤都将进展为雄激素抵抗型前列腺癌（CRPC）或者出现复发甚至转移，有研究表明这些与肿瘤干细胞有关；长链非编码RNA-HOTAIR在多种肿瘤中表达，与肿瘤的恶性进展及肿瘤干细胞的特性有关，我们前期结果发现在前列腺癌恶性细胞及肿瘤干细胞中特异性高表达，是否提示其与前列腺癌进展相关呢，我们将利用FISH原位杂交技术检测前列腺癌中HOTAIR的表达，并试图找到其与临床诊断及预后的关联；肿瘤干细胞中高表达HOTAIR但AR表达缺失，我们将通过CHIP等实验验证HOTAIR是否通过沉默复合体PRC2甲基化AR基因组蛋白从而抑制其表达；最后通过体内外实验，研究HOTAIR是否通过PRC2提高STAT3活性来维持前列腺癌干细胞特性，从而初步揭示HOTAIR在前列

中文关键词： 前列腺癌；长链非编码RNA-HOTAIR；肿瘤干细胞；雄激素受体；肿瘤恶性进展

英文摘要： Prostate cancer (PCa) has become a common and frequent tumour in China， and the majority of cases have been found for late stage. Androgen deprivation therapy (ADT) is still the standard treatment for patients which with advanced tumor, but sooner or later, the tumor will progress into castration resistant prostate cancer (CRPC) or recurrence even metastasis. Studies have shown that these related to the cancer stem cells (CSC); Long noncoding RNA(lncRNA) - HOTAIR expressed in a wide variety of tumors, and the characteristics of malignant progress of tumor and CSC, which is related to our preliminary results that high expression in malignant cells and CSC, whether to prompt its associated with prostate cancer progression? we will use the FISH in situ hybridization technique to detect HOTAIR expression in PCa tissue, and tries to find its correlation with clinical diagnosis and prognosis; High expression of HOTAIR but not AR in CSC, we will utilize experimental verification, such as CHIP PRC2--HOTAIR silence complex to test AR histone methylation; At last, to study whether HOTAIR enhance STAT3 activity to maintain prostate cancer stemness by HOTAIR -PRC2-STAT3 signaling pathway in vivo and in vitro. Together, the study will reveal HOTAIR in prostate cancer and the role in CSC, for tumor recurrence of malignant progression, and also provide new insight and a new method for the treatment of prostate cancer.

英文关键词： prostate cancer;lncRNA-HOTAIR;cancer stem cell;androgen receptor;malignant progression