miR-7 Reverses Breast Cancer Resistance To Chemotherapy By Targeting MRP1 And BCL2

Background: MicroRNAs (miRNAs) are a class of non-coding RNAs that have been linked with breast cancer chemoresistance, which is a major clinical problem causing disease relapse and poor prognosis. miR-7 exerts several tumor suppressive activities.

Purpose: This study was designed to clarify whether and how miR-7 regulates breast cancer chemoresistance.

Methods: miR-7 level in breast cancer was determined by qRT-PCR analysis. Cell viability was assessed by MTS assay to quantify the IC₅₀ value of paclitaxel and carboplatin. The targets of miR-7 were confirmed by luciferase reporter assay.

Results: Higher miR-7 expression predicts better pathological complete response (pCR) of breast cancer patients receiving paclitaxel/carboplatin chemotherapy. In vitro, miR-7 sensitizes breast cancer cell lines (MCF-7 and MDA-MB-231) to paclitaxel and carboplatin, alone and in combination. In addition, we reveal that both the multidrug resistance-associated protein 1 (MRP1) and anti-apoptotic B cell lymphoma 2 (BCL2) are targets of miR-7 in breast cancer cells. Furthermore, miR-7-induced sensitization of breast cancer to paclitaxel/carboplatin is markedly reversed by restoration of MRP1 and BCL2.

Conclusion: These findings show that miR-7 reverses breast cancer chemoresistance through suppressing MRP1 and BCL2, and also suggest that miR-7 may possess a predictive value and represent a therapeutic target in breast cancer chemotherapy.