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通过深度测序对雄激素依赖性和非依赖性前列腺癌细胞系的小 RNA 转录组进行表征。

Characterization of the small RNA transcriptomes of androgen dependent and independent prostate cancer cell line by deep sequencing.

机构信息

Center for Clinical Laboratory Diagnosis, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.

出版信息

PLoS One. 2010 Nov 30;5(11):e15519. doi: 10.1371/journal.pone.0015519.

Abstract

Given the important roles of miRNA in post-transcriptional regulation and its implications for cancer, characterization of miRNA facilitates us to uncover molecular mechanisms underlying the progression of androgen-independent prostate cancer (PCa). The emergence of next-generation sequencing technologies has dramatically changed the speed of all aspects of sequencing in a rapid and cost-effective fashion, which can permit an unbiased, quantitive and in-depth investigation of small RNA transcriptome. In this study, we used high-throughput Illumina sequencing to comprehensively represent the full complement of individual small RNA and to characterize miRNA expression profiles in both the androgen dependent and independent Pca cell line. At least 83 miRNAs are significantly differentially expressed, of which 41 are up-regulated and 42 are down-regulated, indicating these miRNAs may be involved in the transition of LNCaP to an androgen-independent phenotype. In addition, we have identified 43 novel miRNAs from the androgen dependent and independent PCa library and 3 of them are specific to the androgen-independent PCa. Function annotation of target genes indicated that most of these differentially expressed miRNAs tend to target genes involved in signal transduction and cell communication, epically the MAPK signaling pathway. The small RNA transcriptomes obtained in this study provide considerable insights into a better understanding of the expression and function of small RNAs in the development of androgen-independent prostate cancer.

摘要

鉴于 miRNA 在转录后调控中的重要作用及其对癌症的影响,对 miRNA 的特征分析有助于我们揭示雄激素非依赖性前列腺癌 (PCa) 进展的分子机制。新一代测序技术的出现以快速且经济有效的方式极大地改变了测序各个方面的速度,这可以允许对小 RNA 转录组进行无偏、定量和深入的研究。在这项研究中,我们使用高通量 Illumina 测序全面代表单个小 RNA 的完整组成,并对依赖和非依赖雄激素的 PCa 细胞系中的 miRNA 表达谱进行特征分析。至少有 83 个 miRNA 表达水平差异显著,其中 41 个上调,42 个下调,表明这些 miRNA 可能参与了 LNCaP 向雄激素非依赖性表型的转变。此外,我们从依赖和非依赖雄激素的 PCa 文库中鉴定出 43 个新的 miRNA,其中 3 个是雄激素非依赖性 PCa 特有的。靶基因的功能注释表明,这些差异表达的 miRNA 中的大多数倾向于靶向参与信号转导和细胞通讯的基因,尤其是 MAPK 信号通路。本研究中获得的小 RNA 转录组为更好地理解小 RNA 在雄激素非依赖性前列腺癌发展中的表达和功能提供了重要的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd5/2994876/424032d9e9ca/pone.0015519.g001.jpg

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