Contribution of microRNA-3646 to docetaxel resistance in human breast cancer cells by GSK-3β/β-catenin signaling pathway.

Abstract

e12501Background: This study investigated whether mircoRNA profile and miR-3646 regulated sensitivity of breast cancer cells to Docetaxel (Doc). Methods: Doc-resistant MDA-MB-231 breast cancer cell line (MDA-MB-231/Doc) was successfully established in vitro by gradually increasing Doc concentration on the basis of parental MDA-MB-231/S. The potential miRNAs relevant to the drug-resistance was screened by miRNA microarray and confirmed by RT-qPCR. Cell transfection and survival experiments were performed to verify the effect of identified miRNAs on the drug resistance. The miRNA target gene and signal pathway were studied by bioinformatic analyses, RT-qPCR, Western blot and Immunofluorescence test. Results: IC50 of MDA-MB-231/Doc and MDA-MB-231/S to Doc were 22.89μM and 2.75μM, respectively. Compared with MDA-MB-231/S, there were 169 differentially expressed miRNAs in its variant MDA-MB-231/Doc, and miR-3646 was found to be obviously up-regulated. Transfection of miR-3646 mimics into MDA-MB-231/S remarkabl...