Inhibitory Effect of miRNA-145 on PD-L1 Expression in Breast Cancer Cell Line

PD-L1 is one of the most important immune control molecules in breast cancer and plays an important role in suppressing the immune system against tumor cells. Controlling the expression of PD-L1 at mRNA level using miRNA inhibitors could be helpful strategy for cancer treatment. In this study, considering the possible role of miR-145 as a tumor suppression in breast cancer, its involvement in reducing PD-L1 expression in breast cancer cell lines has been investigated.

First, the targeting of miRNA-145 on 3 'UTR of PD-L1 gene was confirmed using bioinformatics software and then by luciferase dual reporter assay. The expression level of miRNA-145 was measured in breast cancer cell lines compared to normal line. After transfection of miRNA-145 into breast cancer cell lines, qRT-PCR was used to evaluate the effect of miRNA-145 on PD-L1 expression.

we showed that decreased expression of miRNA-145 in breast cancer cell lines was directly related to increased PD-L1 expression (r= -0.6175, P value₌0.0457). In addition, increased expression of miRNA-145 in breast cancer cell lines MDA-MB231, BT549 and MCF7 significantly reduced PD-L1 expression (1.938±0.212, 1.784±0.03 and 0.083±0.02 respectively).

Our findings suggest that miRNA-145, by targeting the PD1/PD-L1 pathway and reducing PD-L1 expression, may be a therapeutic agent to prevent the progression of breast cancer.