miR-125b targets erythropoietin and its receptor and their expression correlates with metastatic potential and ERBB2/HER2 expression.
miR-125b targets erythropoietin and its receptor and their expression correlates with metastatic potential and ERBB2/HER2 expression.
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DOI：
10.1186/1476-4598-12-130
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发表时间：
2013-10-28
期刊：
影响因子：
37.3
通讯作者：
Negrini M
中科院分区：
文献类型：
--
作者：
Ferracin M;Bassi C;Pedriali M;Pagotto S;D'Abundo L;Zagatti B;Corrà F;Musa G;Callegari E;Lupini L;Volpato S;Querzoli P;Negrini M
微小RNA 125b是一种具有两面性的基因表达调控因子，既被描述为肿瘤抑制基因（在实体瘤中），又被描述为癌基因（在血液系统恶性肿瘤中）。在人类乳腺癌中，它是下调最显著的微小RNA之一，并且能够调节ERBB2/3的表达。在此，我们在微小RNA模拟物转染后对其在乳腺癌细胞系中的靶标进行了研究。我们检测了已验证的靶标与ERBB2癌基因的相互作用，以及miR - 125b表达与临床变量的相关性。
在MCF7细胞系中转染微小RNA模拟物，并使用安捷伦微阵列和Sylamer生物信息学工具分析基因表达变化后，确定了miR - 125b可能的靶标。通过荧光素酶报告基因实验验证了促红细胞生成素（EPO）及其受体（EPOR）是miR - 125b的靶标，并通过实时定量聚合酶链反应（RT - qPCR）在42例乳腺癌和13例正常样本中评估了它们的表达。通过向MDA - MD - 453和MDA - MB - 157转染ERBB2 RNA并使用RT - qPCR，探索了EPOR和ERBB2转录本之间通过miR - 125b的分子相互作用。
我们确定了一组在miR - 125b转染后下调的基因以及miR - 125b的假定靶标。其中，我们验证了在乳腺癌中经常过表达的促红细胞生成素（EPO）及其受体（EPOR）是miR - 125b的真正靶标。此外，我们探索了与临床变量可能的相关性，发现miR - 125b在转移性乳腺癌中下调，并且EPOR与ERBB2/HER2水平之间存在显著正相关，它们都是miR - 125b的靶标，并作为竞争性内源RNA（ceRNAs）发挥作用。
综上所述，我们的结果显示了乳腺癌中EPO/EPOR和ERBB2共同调节的一种机制，并证实了miR - 125b在控制临床相关癌症特征方面的重要性。
The microRNA 125b is a double-faced gene expression regulator described both as a tumor suppressor gene (in solid tumors) and an oncogene (in hematologic malignancies). In human breast cancer, it is one of the most down-regulated miRNAs and is able to modulate ERBB2/3 expression. Here, we investigated its targets in breast cancer cell lines after miRNA-mimic transfection. We examined the interactions of the validated targets with ERBB2 oncogene and the correlation of miR-125b expression with clinical variables. MiR-125b possible targets were identified after transfecting a miRNA-mimic in MCF7 cell line and analyzing gene expression modifications with Agilent microarrays and Sylamer bioinformatic tool. Erythropoietin (EPO) and its receptor (EPOR) were validated as targets of miR-125b by luciferase assay and their expression was assessed by RT-qPCR in 42 breast cancers and 13 normal samples. The molecular talk between EPOR and ERBB2 transcripts, through miR-125b, was explored transfecting MDA-MD-453 and MDA-MB-157 with ERBB2 RNA and using RT-qPCR. We identified a panel of genes down-regulated after miR-125b transfection and putative targets of miR-125b. Among them, we validated erythropoietin (EPO) and its receptor (EPOR) - frequently overexpressed in breast cancer - as true targets of miR-125b. Moreover, we explored possible correlations with clinical variables and we found a down-regulation of miR-125b in metastatic breast cancers and a significant positive correlation between EPOR and ERBB2/HER2 levels, that are both targets of miR-125b and function as competing endogenous RNAs (ceRNAs). Taken together our results show a mechanism for EPO/EPOR and ERBB2 co-regulation in breast cancer and confirm the importance of miR-125b in controlling clinically-relevant cancer features.
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影响因子：
2.8
作者：
Mrhalová, M;Kodet, R;Hilská, I
通讯作者：
Hilská, I
DOI：
10.1186/bcr2839
发表时间：
2011-03-04
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hannafon BN;Sebastiani P;de las Morenas A;Lu J;Rosenberg CL
通讯作者：
Rosenberg CL
DOI：
10.1073/pnas.0700071104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Laneve, Pietro;Di Marcotullio, Lucia;Caffarelli, Elisa
通讯作者：
Caffarelli, Elisa
影响因子：
11.2
作者：
Saetrom P;Biesinger J;Li SM;Smith D;Thomas LF;Majzoub K;Rivas GE;Alluin J;Rossi JJ;Krontiris TG;Weitzel J;Daly MB;Benson AB;Kirkwood JM;O'Dwyer PJ;Sutphen R;Stewart JA;Johnson D;Larson GP
通讯作者：
Larson GP
影响因子：
4
作者：
Li, W.;Duan, R.;Jin, P.
通讯作者：
Jin, P.