Up-regulation of dicer, a component of the microRNA machinery, in prostate adenocarcinoma
Up-regulation of dicer, a component of the microRNA machinery, in prostate adenocarcinoma
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DOI：
10.2353/ajpath.2006.060480
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发表时间：
2006-11-01
影响因子：
6
通讯作者：
Dhir, Rajiv
中科院分区：
文献类型：
--
作者：
Chiosea, Simion;Jelezcova, Elena;Dhir, Rajiv
MicroRNAs是一种非编码的小分子RNA，由18到24个核苷酸组成，据预测可以调节多达30%的蛋白质编码基因的表达。在前列腺癌中，39个microRNAs表达上调，6个microRNAs表达下调。MicroRNA的生产和功能需要由microRNA机制的蛋白质进行协调处理。DICER是一种RNase M内切酶，是microRNA机制的重要组成部分。从对16例正常前列腺组织、器官受限的前列腺癌和4例转移性前列腺癌的基因阵列分析中，我们发现转移性前列腺癌中microRNA机制的主要组成部分上调，包括迪格尔。对包含232个前列腺样本的组织微阵列的组织化学研究证实，在前列腺上皮内瘤变和81%的前列腺癌中，DICER基因表达上调。前列腺癌组织中DICER水平的升高与临床分期、淋巴结状况和Gleason评分相关。良性和肿瘤性前列腺癌细胞系的蛋白质印迹分析进一步证实了Dier在前列腺癌中表达上调。Dier上调可能解释了前列腺癌中microRNA表达几乎是全局性的增加。上调的microRNA机制的存在可能预测前列腺癌对基于RNA干扰的治疗的易感性。
MicroRNAs are small noncoding; 18- to 24-nt RNAs that are predicted to regulate expression of as many as 30% of protein-encoding genes. in prostate adenocarcinoma, 39 microRNAs are up-regulated, and six microRNAs are down-regulated. Production and function of microRNA requires coordinated processing by proteins of the microRNA machinery. Dicer, an RNase M endonuclease, is an essential component of the microRNA machinery. From a gene array analysis of 16 normal prostate tissue samples, 64 organ-confined, and four metastatic prostate adenocarcinomas, we identified an up-regulation of major components of the microRNA machinery, including Dicer, in metastatic prostate adenocarcinoma. inummohistochemical studies on a tissue microarray consisting of 232 prostate specimens confirmed up-regulation of Dicer in prostatic intraepithelial neoplasia and in 81% of prostate adenocarcinoma. The increased Dicer level in prostate adenocarcinoma correlated with clinical stage, lymph node status, and Gleason score. Western blot analysis of benign and neoplastic prostate cell lines further confirmed Dicer up-regulation in prostate adenocarcinoma. Dicer up-regulation may explain an almost global increase of microRNA expression in prostate adenocarcinoma. The presence of up-regulated microRNA machinery may predict the susceptibility of prostate adenocarcinoma to RNA interference-based therapy.