Role of Tumor Suppressor WWOX in Modulating PD-L1 Expression in Breast Cancers

Objective: This study aimed to determine the potential contribution of WWOX to the regulation of PD-L1 expression in breast cancer.Materials and Methods: MDA-MB-231, MCF-7, and MCF10A cell lines were used in this study. The WWOX gene was overexpressed in MDA-MB-231 cells using the pCMV-WWOX expression vector. In MCF-7 and MCF10A cells, WWOX expression was silenced using siRNA specifically targeting the WWOX gene. WWOX and PD-L1 mRNA expression in each cell group was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), with GAPDH used as the endogenous normalization control. The presence and relative levels of WWOX, PD-L1, and GAPDH proteins were examined by Western blotting.Results: In MDA-MB-231, overexpression of WWOX led to a statistically significant decrease in PD-L1 mRNA levels (p=0.037). In MCF-7 and the non-tumorigenic epithelial cell line MCF10A, transient knockdown of WWOX significantly increased PD-L1 mRNA expression in MCF10A cells (p=0.043), whereas the increase in MCF-7 cells did not show statistical significance (p>0.05). Consistent with the RT-qPCR findings, MDA-MB-231 cells transfected with the pCMVWWOX vector showed increased WWOX protein levels and a concomitant decrease in PD-L1 protein levels.Conclusion: Our findings suggest that the loss of WWOX may enhance tumor immune escape mechanisms via PDL1, particularly in triple-negative breast cancer (TNBC) cells. Clarification of the WWOX/PD-L1 relationship at the molecular and translational levels will require expanded research.