MiR-129-3p promotes docetaxel resistance of breast cancer cells via CP110 inhibition.
Docetaxel is commonly used as an effective chemotherapeutic agent in breast cancer treatment, but the underlying mechanisms of drug resistance are not fully understood. The purpose of this study was to investigate the possible role of miR-129-3p in breast cancer cell resistance to docetaxel. MiR-129 and miR-129-3p inhibitor were transfected into breast cancer cells to investigate their effects on chemoresistance to docetaxel. The function of miR-129-3p was evaluated by apoptosis, cell proliferation, and cell cycle assays. We found that miR-129-3p was up-regulated in MDA-MB-231/Doc cells, concurrent with CP110 down-regulation, compared to the parental MDA-MB-231 cells. In vitro drug sensitivity assays demonstrated that miR-129-3p inhibition sensitized MDA-MB-231/Doc and MCF-7 cells to docetaxel, whereas miR-129 overexpression enhanced MDA-MB-231 and MCF-7 cell resistance to docetaxel. Ectopic miR-129 expression reduced CP110 expression and the luciferase activity of a CP110 3' untranslated region-based reporter construct in MDA-MB-231 cells, suggesting that CP110 is a direct miR-129-3p target. We demonstrated that restoration of CP110 expression in MDA-MB-231 and MCF-7 cells by miR-129 overexpression rendered the cells sensitive to docetaxel. In a nude xenograft model, miR-129 up-regulation significantly decreased MDA-MB-231 cells' response to docetaxel. Our findings suggest that miR-129-3p down-regulation potentially sensitizes breast cancer cells to docetaxel treatment.
The State Key Laboratory of Cancer Biology and Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.|The State Key Laboratory of Cancer Biology and Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, China.
Yuan
Y
Zhang
The State Key Laboratory of Cancer Biology and Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Yu
Y
Wang
The State Key Laboratory of Cancer Biology and Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, China.
Yifang
Y
Wei
The State Key Laboratory of Cancer Biology and Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, China.
Mengyang
M
Li
The State Key Laboratory of Cancer Biology and Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, China.
Shentong
S
Yu
Department of Pulmonary Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Mingxiang
M
Ye
The State Key Laboratory of Cancer Biology and Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Hongmei
H
Zhang
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Suning
S
Chen
The State Key Laboratory of Cancer Biology and Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Wenchao
W
Liu
The State Key Laboratory of Cancer Biology and Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, China.
Jian
J
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D049109:Cell Proliferation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
C467559:CCP110 protein, human; D018797:Cell Cycle Proteins; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C541915:Mirn129 microRNA, human; D010750:Phosphoproteins; D043823:Taxoids; D000077143:Docetaxel