Bioinformatics identification of dysregulated microRNAs in triple negative breast cancer based on microRNA expression profiling.

Bioinformatics identification of dysregulated microRNAs in triple negative breast cancer based on microRNA expression profiling.
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基于microRNA表达谱的生物信息学鉴定三阴性乳腺癌中失调的microRNA

DOI:
10.3892/ol.2017.7707
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发表时间:
2018-03
期刊:
影响因子:
2.9
通讯作者:
Wang X
Wang X
中科院分区:
医学4区
文献类型:
--
作者:
Chen J;Chen Z;Huang J;Chen F;Ye W;Ding G;Wang X

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三阴性乳腺癌(TNBC)约占所有乳腺癌病例的15-20%,与其他乳腺癌亚型相比,通常更具侵袭性,临床结局较差。微小RNA(miRNAs)参与癌症的证据为开发TNBC中的新型有效治疗靶标提供了机会。在本研究中,人乳腺癌细胞系,MDA-MB-231,和MCF-7细胞的miRNA表达谱进行了评估,通过使用miRNA微阵列分析。与MCF-7细胞相比,在MDA-MB-231细胞中共鉴定出107个差异表达的miRNA(57个上调,50个下调)。通过逆转录-定量聚合酶链反应进一步证实了5种显著失调的miRNA(miR-200 c-3 p、miR-221- 3 p、miR-222- 3 p、miR-192- 5 p和miR-146 a)。此外,基因本体分析和途径富集分析显示,发现失调的miRNA和预测的靶点参与促分裂原活化蛋白激酶、Wnt和转化生长因子-β信号传导途径,已知这些途径有助于TNBC进展和转移。最后,miRNA基因网络分析表明,miR-200 c可能是乳腺癌中的关键miRNA。总之,这些发现可以提供TNBC中涉及的异常miRNA的功能的全面视图,并且失调的miRNA有望成为TNBC患者的潜在生物标志物和治疗靶点。
Triple negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancer cases and is usually more aggressive with a poorer clinical outcome compared with other breast cancer subtypes. Evidence of the involvement of microRNAs (miRNAs) in cancer has provided an opportunity for the development of novel effective therapeutic targets in TNBC. In the present study, the miRNA expression profiles of the human breast cancer cell line, MDA-MB-231, and MCF-7 cells, was evaluated by using miRNA microarray analysis. A total of 107 differentially expressed miRNAs (57 upregulated and 50 downregulated) were identified in MDA-MB-231 cells compared with MCF-7 cells. Five prominently dysregulated miRNAs (miR-200c-3p, miR-221-3p, miR-222-3p, miR-192-5p and miR-146a) were further confirmed by reverse transcription-quantitative polymerase chain reaction. In addition, gene ontology analysis and pathway enrichment analysis revealed that the dysregulated miRNAs and predicted targets were found to be involved in the mitogen-activated protein kinase, Wnt, and transforming growth factor-β signaling pathways, which were known to contribute to TNBC progression and metastasis. Finally, miRNA gene network analyses suggested that miR-200c may serve as a crucial miRNA in breast cancer. Taken together, these findings may provide a comprehensive view of the function of aberrant miRNAs involved in TNBC, and dysregulated miRNAs hold promise as potential biomarkers and therapeutic targets for patients with TNBC.
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发表时间: 2012-03
影响因子: 2.5
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