MicroRNA profiling implies new markers of chemoresistance of triple-negative breast cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Center for Cellular and Structural Biology, Guangzhou, Guangdong, People's Republic of China; Department of Clinical Laboratory, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Mao
M
Ouyang
Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Yongxin
Y
Li
Department of Medical Oncology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Sheng
S
Ye
Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Jieyi
J
Ma
Department of Medical Statistics and Epidemiology, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Liming
L
Lu
Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Weiming
W
Lv
Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Guangqi
G
Chang
Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Xiaoxi
X
Li
Center for Cellular and Structural Biology, Guangzhou, Guangdong, People's Republic of China.
Qing
Q
Li
Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Shenming
S
Wang
Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Wenjian
W
Wang
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016000:Cluster Analysis; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D015854:Up-Regulation / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; C547077:MIRN132 microRNA, human; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin