HOTAIR促进PIA恶性进展为前列腺癌的表观遗传机制及调控网络研究

Prostate cancer (PCa) is an important disease affecting the life quality and expectant lifetime of olderly men. At present, some scholars put forward a novel pattern that PCa would be developed from proliferative inflammatory atrophy (PIA). Long noncoding RNA (lncRNA) is involved in the development and metastasis of PCa, which becomes a research hotspot now. However, there is no reports about lncRNA involved in the malignant process of PIA. In preliminary studies, the applicant revealed the correlation between PIA and PCa, and overexpression of lncRNA HOTAIR in PIA and PCa which indicated that HOTAIR might inhibit transcription of tumor suppress genes by modification of histone in target genes. The applicant reasonably hypothesize that HOTAIR promote the malignant process from PIA to PCa through the above mechanism. This study intends to determine whether HOTAIR could be a molecular marker for process and prognosis of PIA and PCa by analyzing correlations between HOTAIR and clinical pathological factors of PIA and PCa, to construct the regulatory network and molecular mechanism of HOTAIR by analyzing the modification of histone in the key genes regulated by HOTAIR, to provide a new therapeutic target to intervene the process of PCa through in vivo and in vitro experiments clarifying the function of HOTAIR.

前列腺癌(PCa)是影响老年男性生活质量和预期寿命的重要疾病。目前有学者提出增生性炎性萎缩(PIA) 恶性进展为PCa可能是PCa发生新模式。长链非编码RNA(lncRNA)参与了PCa发生发展及转移，是目前研究热点。但目前尚无lncRNA参与PIA恶性进展报道。申请者前期研究也证实PIA与PCa密切相关；且在PIA和PCa组织中lncRNA HOTAIR表达均明显上调；HOTAIR可能通过调控靶基因组蛋白修饰，抑制抑癌基因转录。申请者推测HOTAIR可能通过上述机制促进PIA恶性进展为PCa。本研究拟分析PIA及PCa中HOTAIR表达水平与临床病理因素相关性，明确HOTAIR是否可成为进展及预后的分子标志物；并分析HOTAIR对关键性基因表达及其组蛋白修饰调控，明确HOTAIR的调控机制并构建调控网络；进一步通过体内、体外实验明确HOTAIR的功能，为干预PCa疾病进程提供新治疗靶点。