miR3609 sensitizes breast cancer cells to adriamycin by blocking the programmed death-ligand 1 immune checkpoint.

miR3609 sensitizes breast cancer cells to adriamycin by blocking the programmed death-ligand 1 immune checkpoint.
Exp Cell Res. 2019 Mar 20;:
Authors: Li D, Wang X, Yang M, Kan Q, Duan Z
Abstract
Chemoresistance is the leading cause of breast cancer therapy failure, and studies of the mechanisms underlying chemoresistance and the treatment of drug-resistant tumors remain challenging. In the present study, we discovered a novel microRNA, miR3609, that influences the malignancy of breast cancer. Our results showed miR-3609 expression was lower in resistant breast cancer cells than in sensitive breast cancer cells (MCF-7), while PD-L1 expression was higher in resistant breast cancer cells than in sensitive breast cancer cells. Co-transfection of a miR-3609 plasmid with a luciferase construct containing the PD-L1 3'-untranslated region suppressed luciferase activity. Transfection of a miR-3609 mimic markedly suppressed PD-L1 protein expression in MDA-MB-231 and MDA-MB-468 cells in a dose-dependent manner and increased the sensitivity of MCF7/ADR cells to adriamycin, whereas transfection of a miR-3609 inhibitor enhanced PD-L1 protein expression in HBL-100 and MCF-7 cells. In addition, knockdown of PD-L1 by siRNA restored the sensitivity of MCF7/ADR cells to adriamycin. Mice injected with breast cancer cells stably overexpressing miR3609 survived markedly longer and had fewer tumors than mice injected with control miRNA (miR-sc)-transf...

Source: Experimental Cell Research - March 19, 2019 Category: Cytology Authors: Li D, Wang X, Yang M, Kan Q, Duan Z Tags: Exp Cell Res Source Type: research