Introduction of miR-200c as an attenuator of PD-L1 expression in breast cancer cell lines

PD-L1, one of the most important immune-regulating molecules in all cancers including breast cancer, suppresses the immune system against tumor cells. MiRNAs control PD-L1 expression as therapeutic tools and targets. This study investigated the role of miR-200c in reducing PD-L1 expression and breast cancer cell proliferation.

In this study, miR-200c targeting the PD-L1 3'UTR was confirmed by bioinformatics and dual-luciferase assay. PD-L1 expression in breast cancer tissues and cell lines was checked compared to normal tissues and cell lines. qRT-PCR was used to measure PD-L1 expression after miR-200c transfection into breast cancer cell line. The MTT test was used to determine the effect of miR-200c introduction on cell proliferation. 

The 3'UTR region of the PD-L1 gene was identified as a target for miR-200c using bioinformatics software and a dual luciferase assay. The decrease in miR-200c expression in breast cancer cells is directly related to the increase in PD-L1 expression (r =-0.68, P value₌ 0.0158). Also, increasing the expression of miR-200c in MDA-MB231, BT549, and MCF7 breast cancer cells decreased the expression of PD-L1 by (0.217±2.3, 0.021±2.11, and 0.012±0.146, respectively). The increased expression of miR-200c decreased the proliferation rate in MDA-MB231 by 0.45 ± 0.012, BT549 by 0.256 ± 0.2, and in MCF7 by 0.164 ± 0.02, compared to non-transfected cells. (Mean ± SE)

MiR-200c may be able to prevent breast cancer progression by targeting the PD-1/PD-L1 pathway, reducing PD-L1 expression, and reducing breast cancer cell proliferation.