MicroRNA Profiling Implies New Markers of Chemoresistance of Triple-Negative Breast Cancer

Abstract

ObjectiveTriple-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.MethodsIn 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.ResultsWe 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.ConclusionThe 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.

The Dual Regulatory Role of MiR-181a in Breast Cancer

“…Upregulation of miR-181a expression was found in TNBC by three independent research groups where the increased expression of miR-181a correlated with breast cancer aggressiveness [24, 26, 45] (Table 1). Bisso et al investigated the expression of miR-181a in a panel of 104 primary breast cancers and eight normal tissue counterparts.…”

Combined Label-Free Quantitative Proteomics and microRNA Expression Analysis of Breast Cancer Unravel Molecular Differences with Clinical Implications

“…Both miR-205 and miR-342 have been proposed as potential biomarkers for diagnosis of TNBC (35). It has been previously shown that miR125b expression is lower in TNBC tumor tissue when compared with adjacent normal tissue, and has been related with chemoresistance (36). Finally, miR-345 expression was downregulated in ER À breast cancer patients, whereas miR-18a was increased (37).…”

NanoStringDiff: a novel statistical method for differential expression analysis based on NanoString nCounter data

“…miR-374b-5p contributes to gastric cancer cell metastasis and invasion via inhibition of RECK expression (19). miR-181a-5p is elevated in triple negative breast cancer and associates with chemoresistance (20). It is also upregulated in gastric cancer, with positive correlation with lymph node invasion, nerve invasion and vascular invasion (21).…”