title: Circulating microRNA-451 as a predictor of resistance to neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  We aimed to explore the potential application of circulating microRNA-451 (miR-451) in serum in predicting the resistance to neoadjuvant chemotherapy (NACT) in breast cancer (BC).
  
  
  METHODS
  Eighty-two BC patients who underwent NACT were recruited in our study, including 41 NACT-sensitive patients (NACT-sensitive group) and 41 NACT-resistant patients (NACT-resistant group). Additionally, 60 healthy subjects were selected as normal controls. Epirubicin-resistant MCF-7 BC cell line (MCF-7/EPI) and docetaxel-resistant MCF-7 BC cell line (MCF-7/DOC) were cultured in our study. MTT assay was applied to calculate the survival rates of MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells. The expression levels of miR-451 in normal controls, NACT-sensitive group, NACT-resistant group, MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells were measured by qRT-PCR method.
  
  
  RESULTS
  The proliferation rates of both the MCF-7/DOC and MCF-7/EPI cells were significantly restrained at the drug concentration of 10 ng/ml, 50 ng/ml, 100 ng/ml and 200 ng/ml. However, the proliferation rates of MCF-7/DOC and MCF-7/EPI cells both increased significantly at the drug concentration of 500ng/ml. Furthermore, the IC50 of MCF-7/DOC cells was 23.603 ng/ml and the IC50 of MCF-7/EPI cells was 3.209 ng/ml. The relative expression of miR-451 was significantly lower in both the NACT-resistant group and the NACT-sensitive group than the normal control group. We also found that the relative expression level of miR-451 was significantly lower in the NACT-resistant group than that in the NACT-sensitive group. The expression of miR-451 in the MCF-7/EPI and the MCF-7/DOC cell lines was significantly lower than that in the MCF-7 cell lines.
  
  
  CONCLUSIONS
  We supported the view that the relative expression level of miR-451 was lower in the NACT-resistant BC patients, suggesting the circulating miR-451 may have a functional significance in predicting the resistance to NACT in BC patients. We laid a foundation for further research on the resistance to NACT in BC treatment.
authors.forename: Xi
authors.initials: X
authors.lastname: Gu
authors.forename: Jin-Qi
authors.initials: JQ
authors.lastname: Xue
authors.forename: Si-Jia
authors.initials: SJ
authors.lastname: Han
authors.forename: Song-Ying
authors.initials: SY
authors.lastname: Qian
authors.forename: Wen-Hai
authors.initials: WH
authors.lastname: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin
keywords: Breast cancer; circulating serum level; docetaxel-resistant MCF-7 cell line; drug tolerance; epirubicin-resistant MCF-7 cell line; microRNA-451; neoadjuvant chemotherapy