miR-17-5p Circuit Modulates PDL-1 Expression and Atezolizumab Resistance in Triple Negative Breast Cancer (original) (raw)

Background Triple negative breast cancer (TNBC) is an immunogenically hot tumor. The immune checkpoint blockades (ICBs) have been recently emerged as promising therapeutic candidates for several malignancies including TNBC. Yet, the development of innate and/or adaptive resistance by TNBC patients towards ICBs such as programmed death-ligand 1 (PD-L1) inhibitors (e.g. Atezolizumab) shed the light on importance of identifying the underlying mechanisms regulating PD-L1 in TNBC. Recently, it was reported that non-coding RNAs (ncRNAs) perform a fundamental role in regulating PD-L1 expression in TNBC. Hence, this study aims to explore a novel ncRNA axis tuning PD-L1 in TNBC patients and investigate its possible involvement in fighting Atezolizumab resistance. Methods In-silico screening was executed to identify ncRNAs that could eventually target PD-L1. Screening of PD-L1 and the nominated ncRNAs (miR-17-5p, let-7a and CCAT1 lncRNA) was performed in BC tissues and cell lines. Ectopic exp...