Gemcitabine-based
chemotherapy is commonly applied for the treatment of
breast cancer in a clinical setting. However, acquired resistance to
chemotherapy primarily results in treatment failure and eventually culminates in patient mortality. Aberrant expression of
microRNAs (
miRNAs) has been demonstrated to be implicated in the development of chemoresistance; however, the role of miR-873 in the chemoresistance of
breast cancer and its underlying mechanism have not been completely elucidated. Herein, using cell viability assays, the present study demonstrated that overexpression of miR-873 sensitized
triple-negative breast cancer (TNBC) cells (MDA-MB-231 and BT549) towards
gemcitabine treatment, while inhibition of miR-873 promoted resistance of TNBC cells to
gemcitabine exposure. The
3' untranslated region of
zinc finger E-box binding homeobox 1 (ZEB1) was predicted as a candidate target of miR-873, and the regulatory association between ZEB1 and miR-873 was validated with a dual
luciferase assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis confirmed that miR-873 mimics reduced ZEB1 at
mRNA and
protein levels in MDA-MB-231 and BT549 cells. As ZEB1 was previously reported to interact with Yes associated
protein (YAP) to promote
cancer progression. The present study observed that miR-873 overexpression decreased the expression of YAP target genes
AXL receptor tyrosine kinase,
connective tissue growth factor and
cysteine rich angiogenic inducer 61 at
mRNA and
protein levels. Additionally, elevation of the ZEB1 level and reduction of the miR-873 level were detected in
gemcitabine-resistant MDA-MB-231 (MDA-MB-231GEMr) cells, which were accompanied with stronger proliferative ability, compared with parental cells. Overexpression of miR-873 or ZEB1 knockdown reversed chemoresistance of MDA-MB-231GEMr cells by inducing a notable cell growth arrest upon
gemcitabine exposure. In conclusion, the data obtained by the present study demonstrated that the decrease of miR-873 promoted the development of
gemcitabine resistance in TNBC via elevation of ZEB1 expression, which indicated that miR-873 may be a promising predictor for
gemcitabine sensitivity in patients with TNBC.