A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells.
A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells.
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乳腺癌细胞迁移和侵袭过程中 miRNA:mRNA 相互作用的系统评估
DOI：
10.1186/1479-5876-11-57
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发表时间：
2013-03-05
影响因子：
7.4
通讯作者：
Shi H
中科院分区：
文献类型：
--
作者：
Luo D;Wilson JM;Harvel N;Liu J;Pei L;Huang S;Hawthorn L;Shi H
在这项研究中，我们进行了一个系统的评估与乳腺癌细胞的侵袭性相关的功能miRNA-mRNA的相互作用，使用整合的miRNA和mRNA表达谱，生物信息学预测和功能分析的组合。miRNA表达分析鉴定出11个差异表达的miRNA，包括7个下调的miRNA。（miR-200 c、miR-205、miR-203、miR-141、miR-34 a、miR-183和miR-375）和4种上调的miRNA（miR-146 a、miR-138、miR-125 b1和miR-100）在侵袭性细胞系中的表达。将miR-200 c、miR-205和miR-375模拟物转染到MDA-MB-231细胞中可抑制体外细胞迁移和侵袭。通过对miR-200 c、miR-205和miR-375的miRNA和mRNA表达的综合分析，确定了35个已知和新的miR-200 c、miR-205和miR-375靶基因，包括CFL 2、LAMC 1、TIMP 2、ZEB 1、CDH 11、PRKCA、PTPRJ、PTPRM、LDHB和SEC 23 A。令人惊讶的是，这些基因中的大多数（27个基因）是miR-200 c的靶基因，这表明miR-200 c在调节乳腺癌细胞的侵袭性中起着关键作用。我们对miR-200 c的靶基因之一CFL 2进行了表征，并证明CFL 2在侵袭性乳腺癌细胞系中过表达，且可被外源性miR-200 c显著下调。组织芯片分析进一步揭示了原发性乳腺癌组织中CFL 2的表达与肿瘤分级相关。从这项研究中获得的结果可能会提高我们对这些候选miRNAs及其靶基因在乳腺癌侵袭性中的作用的理解，并最终导致与预后相关的新生物标志物的鉴定。
In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the invasiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in invasive cell lines when compared to normal and less invasive cell lines. Transfection of miR-200c, miR-205, and miR-375 mimics into MDA-MB-231 cells led to the inhibition ofin vitrocell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, includingCFL2,LAMC1,TIMP2,ZEB1,CDH11,PRKCA,PTPRJ,PTPRM,LDHB, andSEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that miR-200c plays a pivotal role in regulating the invasiveness of breast cancer cells. We characterized one of the target genes of miR-200c,CFL2, and demonstrated thatCFL2is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer invasiveness and ultimately lead to the identification of novel biomarkers associated with prognosis.
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影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
3.7
作者：
Al-Alwan M;Olabi S;Ghebeh H;Barhoush E;Tulbah A;Al-Tweigeri T;Ajarim D;Adra C
通讯作者：
Adra C
影响因子：
11.2
作者：
Hurst DR;Edmonds MD;Scott GK;Benz CC;Vaidya KS;Welch DR
通讯作者：
Welch DR
影响因子：
3.7
作者：
Enerly E;Steinfeld I;Kleivi K;Leivonen SK;Aure MR;Russnes HG;Rønneberg JA;Johnsen H;Navon R;Rødland E;Mäkelä R;Naume B;Perälä M;Kallioniemi O;Kristensen VN;Yakhini Z;Børresen-Dale AL
通讯作者：
Børresen-Dale AL
影响因子：
4.3
作者：
Hurteau, Gregory J.;Spivack, Simon D.;Brock, Graham J.
通讯作者：
Brock, Graham J.