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

• Main Authors: Hong T, Ding J, Li W
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-12-01
• Series: OncoTargets and Therapy
• Subjects: mir-7; breast cancer; pathological complete response; chemoresistance; mrp1; bcl2
• Online Access: https://www.dovepress.com/mir-7-reverses-breast-cancer-resistance-to-chemotherapy-by-targeting-m-peer-reviewed-article-OTT

Tianzi Hong,1 Jian Ding,2 Wenlian Li2 1Department of Thyroid and Breast Surgery, Jinjiang Hospital of Quanzhou Medical College, Jinjiang 362200, People’s Republic of China; 2Department of Breast Surgery, Zhongshan Hospital of Xiamen University, Xiamen 361004, People’s Republic of ChinaCorrespondence: Wenlian LiDepartment of Breast Surgery, Zhongshan Hospital of Xiamen University, No. 201 South Hubin Street, Siming District, Xiamen 361004, People’s Republic of ChinaTel [phone]Email [e-mail]: 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.Keywords: miR-7, breast cancer, pathological complete response, chemoresistance, MRP1, BCL2