MicroRNA-205-directed transcriptional activation of tumor suppressor genes in prostate cancer.
MicroRNA-205-directed transcriptional activation of tumor suppressor genes in prostate cancer.
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DOI：
10.1002/cncr.25488
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发表时间：
2010-12-15
期刊：
影响因子：
6.2
通讯作者：
Dahiya, Rajvir
中科院分区：
文献类型：
--
作者：
Majid, Shahana;Dar, Altaf A.;Saini, Sharanjot;Yamamura, Soichiro;Hirata, Hiroshi;Tanaka, Yuichiro;Deng, Guoren;Dahiya, Rajvir
microRNA（miRNAs）是一种小的非编码RNA，调节约30%的人类基因的表达。它们在许多细胞过程中发挥重要作用，包括发育、增殖和凋亡。目前认为，miRNA通过沉默靶基因的表达来引起它们的作用。在这里，我们发现microRNA-205（miR-205）通过靶向其启动子中的特定位点诱导IL 24和IL 32肿瘤抑制基因的表达。本研究采用的方法包括小RNA转染、实时定量PCR、原位杂交、荧光标记原位杂交、细胞周期、凋亡、细胞活力、迁移、克隆和侵袭试验、免疫印迹、荧光素酶报告、核运行和染色质免疫沉淀试验。我们的研究结果表明，miR-205在前列腺癌中是沉默的。它的重新表达诱导细胞凋亡和细胞周期阻滞。它还损害前列腺癌细胞的生长、迁移、克隆性和侵袭性。MicroRNA-205在mRNA和蛋白水平诱导肿瘤抑制基因IL 24和IL 32。观察到响应于miR-205的IL 24和IL 32基因中转录活性启动子的体外转录诱导和标记物富集。在这项研究中，我们确定了一个新的功能，miR-205特异性激活肿瘤抑制基因的启动子中的特定位点的目标。这些结果证实了miRNAs在转录水平上调节基因表达的新功能。肿瘤抑制基因的特异性激活（例如，IL 24、IL 32）或其他失调基因的表达可能有助于前列腺癌治疗的新方法。
MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of approximately 30% of all human genes. They play important roles in numerous cellular processes including development, proliferation, and apoptosis. It is currently believed that miRNAs elicit their effect by silencing the expression of target genes. Here we show that microRNA-205 (miR-205) induces the expression of IL24 and IL32 tumor suppressor genes by targeting specific sites in their promoters. Methods used in this study include transfection of small RNAs, quantitative-real-time-PCR, in-situ hybridization, fluorescence labeled in-situ hybridization, cell cycle, apoptosis, cell viability, migratory, clonability and invasion assays, immunoblotting, luciferase reporter, nuclear run-on and chromatin immunoprecipitation assays. Our results revealed that miR-205 is silenced in prostate cancer. Its re-expression induced apoptosis and cell cycle arrest. It also impaired cell growth, migration, clonability and invasiveness of prostate cancer cells. MicroRNA-205 induced tumor suppressor genes IL24 and IL32 at both mRNA and protein levels. Induction of in-vitro transcription and enrichment of markers for transcriptionally active promoters in IL24 and IL32 genes was observed in response to miR-205. In this study we identify a new function for miR-205 to specifically activate tumor suppressor genes by targeting specific sites in their promoters. These results corroborate a new function that miRNAs have in regulating gene expression at the transcriptional level. The specific activation of tumor suppressor genes (e.g., IL24, IL32) or other dysregulated genes by microRNAs may contribute to the novel therapeutic approach in the treatment of prostate cancer.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
DOI：
10.1073/pnas.0808830105
发表时间：
2008-10-21
影响因子：
11.1
作者：
Kim, Daniel H.;Saetrom, Pal;Rossi, John J.
通讯作者：
Rossi, John J.
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
11.2
作者：
Majid, Shahana;Kikuno, Nobuyuki;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir