miR‑125b regulates the drug‑resistance of breast cancer cells to doxorubicin by targeting HAX‑1

Abstract

MircroRNAs (miRNAs) are considered as essential regulators in the tumorigenesis and chemoresistance of multiple cancer types. In the present study, it was demonstrated that the expression levels of miR‑125b were significantly downregulated in the tissues of patients with breast cancer (BC), as well as the BC cell lines in vitro. To study the association between chemoresistance and miR‑125b in BC, doxorubicin (DOX)‑resistant MCF‑7 (MCF‑7/R) cells were established, and gain‑ and loss‑of‑function experiments were performed. It was demonstrated that the overexpression of miR‑125b increased the sensitivity of MCF‑7/R cells to DOX. Furthermore, it was revealed that the sensitization of miR‑125b mimics to DOX‑induced cell death was regulated by the hematopoietic cell‑specific protein 1‑associated protein X‑1 (HAX‑1) vector and HAX‑1 small interfering RNA. These results emphasized the notable function of miR‑125b and its target of HAX‑1 in regulating DOX‑resistance. In addition, it was demonstrated that the miR‑125b mimics promoted the loss of the mitochondrial membrane potential and the generation of reactive oxygen species induced by DOX treatment in MCF‑7/R cells. These data suggest that the miR‑125b‑HAX‑1‑mitochondria pathway has a notable function in the treatment of DOX‑resistant BC cells, which may provide a novel target for the chemotherapy of BC.