MiR-200c and HuR in ovarian cancer.
MiR-200c and HuR in ovarian cancer.
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DOI：
10.1186/1471-2407-13-72
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发表时间：
2013-02-08
期刊：
影响因子：
3.8
通讯作者：
Ferlini C
中科院分区：
文献类型：
--
作者：
Prislei S;Martinelli E;Mariani M;Raspaglio G;Sieber S;Ferrandina G;Shahabi S;Scambia G;Ferlini C
实体恶性肿瘤中的microRNA可以作为预后良好或不良的预测因子。这是miR-200家族成员的情况，miR-200家族成员是上皮向间充质转化的主要调节因子，并且据报道充当癌基因和肿瘤抑制因子。本研究评估了miR-200 c作为III类β-微管蛋白（TUBB 3）调节剂的作用，TUBB 3是卵巢癌耐药和预后不良的相关因素。在一组具有固有或获得性耐药的卵巢癌细胞系中评估miR-200 c的表达。在A2780和Hey细胞系中获得了miR-200 c的稳定过表达。采用交联偶联亲和纯化法和核糖核酸免疫沉淀法对miR-200 c、HuR与TUBB 3 mRNA 3′UTR之间的复合物进行鉴定。应用纳米流控技术和免疫组化技术检测220例卵巢癌组织中HuR、TUBB 3和miR-200 c的表达。在一组卵巢腺癌细胞系中，我们观察到miR-200 c表达与化疗耐药性之间存在直接相关性。在A2780细胞中，miR-200 c靶向TUBB 3 3′UTR，而在大多数其他细胞系中，miR-200 c与TUBB 3表达呈正相关。通过对3′ UTR相关复合物的分析，我们发现miR-200 c可以增加RNA结合蛋白HuR与TUBB 3 mRNA的结合，而HuR结合增强TUBB 3 mRNA的翻译。最重要的是，在我们对220例卵巢癌患者的分析中，我们观察到miR-200 c的过表达与取决于HuR的细胞定位的不良或良好结果相关。这项研究提出了一个模型，miR-200 c和HuR对卵巢癌中TUBB 3表达的联合调节活性。当HuR在细胞核中时，miR-200 c的高表达抑制TUBB 3表达并导致良好的预后，而当HuR在细胞质中时，相同的miRNA增强TUBB 3表达并产生不良预后。这些发现揭示了多维分析在研究miRNA表达的预后作用中的有用性。
MicroRNAs in solid malignancies can behave as predictors of either good or poor outcome. This is the case with members of the miR-200 family, which are the primary regulators of the epithelial to mesenchymal transition and have been reported to act as both oncogenes and tumor suppressors. This study assessed the role of miR-200c as regulator of class III β-tubulin (TUBB3), a factor associated with drug-resistance and poor prognosis in ovarian cancer. Expression of miR-200c was assessed in a panel of ovarian cancer cell lines with inherent or acquired drug-resistance. Stable overexpression of miR-200c was obtained in A2780 and Hey cell lines. Crosslinking-coupled affinity purification method and ribonucleic-immunoprecipitation assay were used to characterise the complexes between miR-200c, HuR and 3′UTR region of TUBB3 mRNA. Nanofluidic technology and immunohistochemistry were used to analyze the expression of HuR, TUBB3 and miR-200c in 220 ovarian cancer patients. In a panel of ovarian adenocarcinoma cell lines, we observed a direct correlation between miR-200c expression and chemoresistance. In A2780 cells miR-200c targeted TUBB3 3′UTR, while a positive correlation was observed between miR-200c and TUBB3 expression in most of the other cell lines. Through the analysis of 3′UTR-associated complexes, we found that the miR-200c can increase the association of the RNA binding protein HuR with TUBB3 mRNA, whereas HuR binding enhanced TUBB3 mRNA translation. Most importantly, in our analysis on 220 ovarian cancer patients we observed that overexpression of miR-200c correlated with poor or good outcome depending on the cellular localization of HuR. This study suggests a model for the combined regulatory activity of miR-200c and HuR on TUBB3 expression in ovarian cancer. When HuR is nuclear, high expression of miR-200c inhibits TUBB3 expression and results in a good prognosis, whereas when HuR occurs in cytoplasm, the same miRNA enhances TUBB3 expression and produces a poor outcome. These findings reveal the usefulness of multidimensional analysis in the investigation of the prognostic role of miRNA expression.
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影响因子：
16
作者：
Mukherjee N;Corcoran DL;Nusbaum JD;Reid DW;Georgiev S;Hafner M;Ascano M Jr;Tuschl T;Ohler U;Keene JD
通讯作者：
Keene JD
影响因子：
11.2
作者：
Raspaglio, Giuseppina;De Maria, Ilaria;Ferlini, Cristiano
通讯作者：
Ferlini, Cristiano
影响因子：
3.5
作者：
Raspaglio, Giuseppina;Filippetti, Flavia;Ferlini, Cristiano
通讯作者：
Ferlini, Cristiano
影响因子：
11.5
作者：
Nam, Eun Ji;Yoon, Heejei;Kim, Sunghoon
通讯作者：
Kim, Sunghoon
影响因子：
11.2
作者：
Mozzetti, Simona;Iantomasi, Raffaella;Ferlini, Cristiano
通讯作者：
Ferlini, Cristiano