MicroRNA profiling implies new markers of chemoresistance of triple-negative breast cancer.
MicroRNA profiling implies new markers of chemoresistance of triple-negative breast cancer.
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DOI：
10.1371/journal.pone.0096228
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Ouyang M;Li Y;Ye S;Ma J;Lu L;Lv W;Chang G;Li X;Li Q;Wang S;Wang W
患有真正化学敏感疾病的三阴性乳腺癌（TNBC）患者在所有TNBC患者中仍然占少数。本研究的目的是鉴定与TNBC化学抗性相关的microRNA（miRNAs）。本研究利用microRNA芯片对三阴性乳腺癌（triple-negative breast cancer，TNBC）和正常乳腺组织中的miRNAs进行了比较。采用实时定量PCR（qRT-PCR）方法检测特异性去调控miRNAs的变化趋势。我们使用starBase 2.1和GOrilla来预测特定miRNA的潜在靶点。采用细胞活力和凋亡测定来确定TNBC细胞中特异性miRNA的改变对化学敏感性的影响。我们鉴定了11种特异性去调控的miRNA，包括5种上调的miRNA（miR-155- 5 p、miR-21- 3 p、miR-181 a-5 p、miR-181 b-5 p和miR-183- 5 p）和6种下调的miRNA（miR-10 b-5 p、miR-451 a、miR-125 b-5 p、miR-31- 5 p、miR-195- 5 p和miR-130 a-3 p）。此后，通过qRT-PCR确认该结果。我们预测了候选miRNAs的潜在靶点，发现它们参与了癌症相关的通路。我们首次发现miR-130 a-3 p和miR-451 a在TNBC中下调。11个特异性去调控的miRNAs中有9个与化疗耐药性相关。在体外实验中，我们发现MDA-MB-231细胞中miR-130 a-3 p或miR-451 a的上调显著改变了细胞对阿霉素的敏感性。结果表明，TNBC化疗可能受到一组miRNA的影响。TNBC中miRNAs的异常表达主要与化疗耐药有关。这可能是TNBC可能逃避化疗导致早期复发和高死亡风险的部分原因。改变它们的表达状态可能是改善TNBC患者化疗结果的潜在治疗策略。
Triple-negative breast cancer (TNBC) patients with truly chemosensitive disease still represent a minority among all TNBC patients. The aim of the present study is to identify microRNAs (miRNAs) that correlate with TNBC chemoresistance. In this study, we conducted miRNAs profile comparison between triple-negative breast cancer (TNBCs) and normal breast tissues by microRNA array. Quantitative real-time PCR (qRT-PCR) was utilized to confirm the specific deregulated miRNAs change trend. We used starBase 2.1 and GOrilla to predict the potential targets of the specific miRNAs. Cells viability and apoptosis assays were employed to determine the effect of alteration of the specific miRNAs in TNBC cells on the chemosensitivity. We identified 11 specific deregulated miRNAs, including 5 up-regulated miRNAs (miR-155-5p, miR-21-3p, miR-181a-5p, miR-181b-5p, and miR-183-5p) and 6 down-regulated miRNAs (miR-10b-5p, miR-451a, miR-125b-5p, miR-31-5p, miR-195-5p and miR-130a-3p). Thereafter, this result was confirmed by qRT-PCR. We predicted the potential targets of the candidate miRNAs and found that they are involved in cancer-associated pathways. For the first time, we found that miR-130a-3p and miR-451a were down-regulated in TNBC. 9 of the 11 specific deregulated miRNAs were found to be associated with chemoresistance. In vitro assays, we found that up-regulation of either miR-130a-3p or miR-451a in MDA-MB-231 cells significantly changed the cells sensitivity to doxorubicin. The results suggest that TNBC chemotherapy might be affected by a cluster of miRNAs. The abnormal expression miRNAs in TNBC are mainly chemoresistance related. This might be part of reason that TNBC likely to evade from chemotherapy resulting in early relapse and high risk of death. To alter their expression status might be a potential therapeutic strategy to improve the outcome of chemotherapy for TNBC patients.
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