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

Abstract

Introduction: 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. Methods: 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.Results: 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). Conclusion: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.

Targeting long non-coding RNA MALAT1 reverses cancerous phenotypes of breast cancer cells through microRNA-561-3p/TOP2A axis

“…Through post-transcriptional regulation 37 , processing, mRNA splicing 38 , translation, or post-translational protein modification, long non-coding RNAs can also influence cell homeostasis. Additionally, it influences mRNA through the binding of microRNA, which lowers the amount of short free RNA and lessens the impact on transcript coding 39 , 40 . The balance of metabolic activities is necessary for proper cell function.…”