前列腺癌课件.pptx

TMPRSS2-ERG Gene Fusions induce prostate tumorigenesis through modulating microRNA miR-200c TMPRSS2-ERG基因融合通过调节miR-200c诱导前列腺肿瘤形成 Oncogene Impact factor:8.559 PCa: prostate cancer 前列腺癌 TMPRSS2: transmembrane protease, serine 2 横跨膜的蛋白 酶，丝氨酸2 ETS: erythroblast transformation-specific特异性有核红血球 EMT: epithelial-to-mesenchymal transition 上皮间叶细胞转化 Polycomb group proteins: 多梳家族蛋白(表观遗传调控因子 polycomb复合蛋白被认为与多种肿瘤的发生发展有极大相关 性，其中Rnf2在多种肿瘤中呈高表达。) Abbreviations Background Chromosomal translocations that juxtapose the androgen-sensitive promoter of the TMPRSS2 gene to the coding region of the oncogenic ETS family transcription factor ERG termed TMPRSS2-ERG gene fusions, have been found in 40–80% of PCa. 在40-80%的前列腺癌中出现TMPRSS2-ERG基因融合，这种基因融合将 雄激素敏感的启动子TMPRSS2基因和编码区致癌ETS家族转录因子ERG 融合的染色体易位称为TMPRSS2-ERG基因融合 Ø Gordanpour et al. found that miR-221 is down-regulated in patients with tumors bearing TMPRSS2-ERG gene fusions.However, no mechanistic studies were carried out to determine whether and how ERG regulates miR-221 expression. Ø Hart et al. showed that miR-145 inhibits ERG expression by directly targeting its 3′UTR. Loss of miR-145 may provide a TMPRSS2-ERG gene fusion-independent means to ERG up-regulation in PCa. Background Introduction Purpose: Identify miRNAs that are downstream of ERG and nominate miR -200c as a robust and important ERG-regulated miRNA. The loss of miR-200c is linked to poor differentiation(低分化) and stem cell-like cancer cells and is regulated by DNA methylation, oncogene activation, or loss of tumor suppressor genes such as p53. Functional studies have clearly demonstrated essential roles of miR-200c in suppressing EMT and inhibiting metastasis of various cancer types. Mechanistically, this is mediated by reciprocal repression of miR-200c and ZEB1, a critical mediator and activator of EMT. Introduction Reconstitution or expression of miR-200c has been attemp