Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients
Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients
复制标题
DOI：
10.1038/modpathol.2008.33
复制
发表时间：
2008-06-01
期刊：
影响因子：
7.5
通讯作者：
O'Leary, John J.
中科院分区：
文献类型：
--
作者：
Flavin, Richard J.;Smyth, Paul C.;O'Leary, John J.
MicroRNA 是一组长度约为 22 个核苷酸的小型非编码 RNA。最近的研究表明成熟 microRNA 在人类癌症中存在差异表达。 microRNA 的产生和功能需要 microRNA 机器的蛋白质进行协调处理。 Dicer 和 Drosha（RNase III 核酸内切酶）是 microRNA 机器的重要组成部分。最近，核糖体抗结合因子 eIF6 也被发现在 microRNA 介导的转录后沉默中发挥作用。我们表征了卵巢浆液性癌中 microRNA 机制蛋白编码基因表达的变化。在 66 个卵巢浆液性癌的组织微阵列中对 eIF6 和 Dicer 的蛋白表达进行了定量。使用定量逆转录 PCR 对一组独立的 50 个福尔马林固定、石蜡包埋的卵巢浆液性癌样品分析 Dicer、Drosha 和 eIF6 mRNA 表达。 eIF6 和 Dicer 的表达谱与临床病理学和患者生存数据相关。我们提供明确的证据表明，eIF6 和 Dicer 在相当大比例的卵巢浆液性癌中均上调，并且与特定的临床病理特征相关，最显着的是 eIF6 低表达与无病生存率降低相关。 eIF6 和 microRNA 机制蛋白质的状态可能有助于预测未来基于干扰 RNA 的治疗的毒性和敏感性。
MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. Production and function of microRNAs require coordinated processing by proteins of the microRNA machinery. Dicer and Drosha (RNase III endonucleases) are essential components of the microRNA machinery. Recently, the ribosome anti-association factor eIF6 has also been found to have a role in microRNA-mediated post-transcriptional silencing. We characterized the alterations in the expression of genes encoding proteins of microRNA machinery in ovarian serous carcinoma. Protein expression of eIF6 and Dicer was quantified in a tissue microarray of 66 ovarian serous carcinomas. Dicer, Drosha and eIF6 mRNA expression was analysed using quantitative reverse transcription-PCR on an independent set of 50 formalin-fixed, paraffin-embedded ovarian serous carcinoma samples. Expression profiles of eIF6 and Dicer were correlated with clinicopathological and patient survival data. We provide definitive evidence that eIF6 and Dicer are both upregulated in a significant proportion of ovarian serous carcinomas and are associated with specific clinicopathological features, most notably low eIF6 expression being associated with reduced disease-free survival. The status of eIF6 and proteins of the microRNA machinery may help predict toxicity and susceptibility to future interfering RNA-based therapy.