The miRNA-4330/ABCG2 axis overcomes drug resistance and cancer progression in both ER-positive and ER-negative resistant breast cancer cells.

[BACKGROUND]  This study sought to uncover novel targets for fighting drug resistance in breast cancer therapy, such as miRNA that target ABC transporters and decrease the oncogenic activity of breast cancer cells.

[METHODS] MiRNA ABC transporter targets were predicted using in silico methods after evaluating the ABC transporter route. In addition, miRNA expression, gene annotation, and gene ontology concepts were investigated. The expression levels of ABC transporter genes and miRNAs were determined using QRT-PCR. Dual luciferase activity was assessed to establish the precise ABC transporter-specific interaction. Flowcytometric analysis was used to detect doxorubicin uptake in miR-4330-treated cells, as well as cell cycle analyses. The spreading capacity of miR-4330-upregulated cells was investigated.

[RESULTS] The current study identified miR-4330 as an anti-drug and anti-oncogenic molecule in both estrogen receptor positive and negative breast cancer cells. Furthermore, the study identified the mechanism by which miR-4330 restoration reduces drug resistance by drastically decreasing ABCG2 expression (fold change of -0.25), which was accompanied by a considerable increase in doxorubicin accumulation or influx in both cell lines. Furthermore, miRNA-4330 restoration resulted in a considerable reduction in metastatic and spreading capabilities in both cell types.

[CONCLUSION] The current findings identified miR-4330 restoration as a tool for overcoming acquired drug resistance and reducing cancer activity, which might be used to improve therapeutic strategies and treatment regimens for breast cancer patients. miR-4330 may be useful as a diagnostic and prognostic marker for drug-resistant breast cancer.