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.
Highlights
Primary breast cancer is usually classified into different categories based on the gene expression profile, phenotype and susceptibility to therapy
Triple-negative breast cancer (TNBC) is a kind of invasive carcinoma of primary breast cancer that lacking expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), which accounts for about 12–17% of all breast cancers including patients with stage I–IV breast cancer
This study aimed to identify tumor-specific miRNAs which might involve in TNBC carcinogenesis and chemotherapy by miRNA profile comparison between TNBCs and normal breast tissues
Summary
Primary breast cancer is usually classified into different categories based on the gene expression profile, phenotype and susceptibility to therapy. TNBC is a kind of invasive carcinoma of primary breast cancer that lacking expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), which accounts for about 12–17% of all breast cancers including patients with stage I–IV breast cancer. Since the expressions of ER, PR and HER2/neu conventionally determine the therapeutic response and general disease prognosis of primary breast cancer, methods for the treatment of TNBC patients are still limited in clinical. TNBC patients with truly chemosensitive disease still represent a minority among all TNBC patients [2,3]. To identify the subgroup of TNBC patients with chemosensitive disease and predict biomarkers for personalizing use of chemotherapy is of great value to improve the prognosis of TNBC patients
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