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首页> 外文期刊>PLoS One >Expression and function of the miR-143/145 cluster in vitro and in vivo in human breast cancer
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Expression and function of the miR-143/145 cluster in vitro and in vivo in human breast cancer

机译：miR-143 / 145簇在人乳腺癌中的体内外表达和功能

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MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and are dysregulated in cancer. Studies of miRNAs to explore their potential as diagnostic and prognostic markers are of great scientific interest. Here, we investigate the functional properties and expression of the miR-143/145 cluster in breast cancer (BC) in vitro and in vivo. The ER positive MCF7, the HER2 positive SK-BR-3, and the triple negative cell line MDA-MB-231 were used to assess cell proliferation and cell invasion. Expression of miRNA in 108 breast cancers in the Norwegian Women and Cancer Study and 44 benign tissue controls were analyzed by microarray and validated by RT-PCR. Further, in situ hybridization (ISH) was used to study the cellular and subcellular distribution of the miRNAs. In vitro, miR-143 promoted proliferation of MCF7 and MDA-MB-231 cells, whereas miR-145 and the cotransfection of both miRNAs inhibited proliferation in all three cell lines. The cells’ invasive capacity was reduced after transfection and cotransfection of the miRNAs. In line with the tumor suppressive functions in vitro, the expression of miR-143 and miR-145 was lower in malignant compared to benign breast tissue, and lower in the more aggressive tumors with higher tumor grade, loss of ER and the basal-like phenotype. ISH revealed miR-143 to be cytoplasmatic and predominantly expressed in luminal cells in benign tissue, whilst miR-145 was nuclear and with strong staining in myoepithelial cells. Both miRNAs were present in malignant epithelial cells and stromal fibroblasts in BC. This study demonstrates that miR-143 and -145 have functional properties and expression patterns typical for tumor suppressors, but the function is influenced by cellular factors such as cell type and miRNA cotransfection. Further, the nuclear functions of miR-145 should be explored for a more complete understanding of the complexity of miRNA regulation and function in BC.
机译：微小RNA（miRNA）是小的非编码RNA，可充当基因表达的转录后调节子，并在癌症中失调。研究miRNA来探索其作为诊断和预后标志物的潜力具有重大的科学兴趣。在这里，我们研究了miR-143 / 145簇在体外和体内在乳腺癌（BC）中的功能特性和表达。 ER阳性MCF7，HER2阳性SK-BR-3和三阴性细胞系MDA-MB-231用于评估细胞增殖和细胞侵袭。通过微阵列分析和在RT-PCR中验证了在《挪威妇女与癌症研究》中108个乳腺癌和44个良性组织对照中miRNA的表达。此外，原位杂交（ISH）用于研究miRNA的细胞和亚细胞分布。在体外，miR-143促进了MCF7和MDA-MB-231细胞的增殖，而miR-145和两种miRNA的共转染抑制了这三种细胞系的增殖。转染和共转染miRNA后，细胞的侵袭能力降低。与体外肿瘤抑制功能相一致，与良性乳腺组织相比，miR-143和miR-145在恶性肿瘤中的表达较低，而在肿瘤分级更高，ER丧失和基底样病变的更具侵袭性的肿瘤中，miR-143和miR-145的表达较低。表型。 ISH显示miR-143是细胞质的，并且主要在良性组织的腔细胞中表达，而miR-145是有核的并且在肌上皮细胞中具有强染色。两种miRNA均存在于卑诗省的恶性上皮细胞和基质成纤维细胞中。这项研究表明，miR-143和-145具有典型的肿瘤抑制基因的功能特性和表达模式，但其功能受细胞因子（例如细胞类型和miRNA共转染）的影响。此外，应探索miR-145的核功能，以更全面地了解BC中miRNA调控和功能的复杂性。

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