miR-21 targets 15-PGDH and promotes cholangiocarcinoma growth.
miR-21 targets 15-PGDH and promotes cholangiocarcinoma growth.
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DOI：
10.1158/1541-7786.mcr-13-0419
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Wu T
中科院分区：
文献类型：
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作者：
Lu L;Byrnes K;Han C;Wang Y;Wu T
MicroRNAs （miRs）是一组小的非编码rna，通过结合靶mRNA中的特定靶位点来调节基因的翻译。本研究探讨了microRNA-21 （miR-21）在人胆管癌中的生物学功能和分子机制。人胆管癌标本的原位杂交分析显示，与非癌性胆道上皮相比，胆管癌组织中的miR-21增加。miR-21的慢病毒转导增强了体外人胆管癌细胞的生长和克隆效率，而miR-21的抑制则降低了这些参数。在体内异种移植模型系统中，miR-21的过表达也促进了胆管癌的生长。NAD+连接的15-羟基前列腺素脱氢酶（15-PGDH/HPGD）是将致瘤性前列腺素E2 （PGE2）转化为其生物无活性代谢物的关键酶，被确定为胆管癌细胞中miR-21的直接靶点。与此同时，环氧化酶-2 （COX2）过表达和PGE2处理增加了人胆管癌细胞中miR-21水平并增强了miR-21启动子活性。
MicroRNAs (miRs) are a group of small, non-coding RNAs that modulate the translation of genes by binding to specific target sites in the target mRNA. This study investigated the biological function and molecular mechanism of microRNA-21 (miR-21) in human cholangiocarcinoma. In situ hybridization analysis of human cholangiocarcinoma specimens showed increased miR-21 in cholangiocarcinoma tissue compared to the non-cancerous biliary epithelium. Lentiviral transduction of miR-21 enhanced human cholangiocarcinoma cell growth and clonogenic efficiency in vitro, whereas inhibition of miR-21 decreased these parameters. Over-expression of miR-21 also promoted cholangiocarcinoma growth using an in vivo xenograft model system. The NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH/HPGD), a key enzyme that converts the protumorigenic prostaglandin E2 (PGE2) to its biologically inactive metabolite, was identified as a direct target of miR-21 in cholangiocarcinoma cells. In parallel, cyclooxygenase-2 (COX2) over-expression and PGE2 treatment increased miR-21 levels and enhanced miR-21 promoter activity in human cholangiocarcinoma cells.