OR7E47P regulates TGF-β secretion of fibroblast via ROBO2 pathway to modulate the TME in NSCLC

Whereas the role of OR7E47P in NSCLC is not clear, we explored the impact of OR7E47P on the prognosis of NSCLC patients and possible mechanisms through bioinformatics and experi-mental approaches. OR7E47P, underexpressed in NSCLC tumor tissues, is associated with better prognosis and enhanced immune benefits. Localization analyses showed OR7E47P may func-tions as a cytoplasmic processing pseudogene, regulating ROBO2 expression via the OR7E47P/miR-183-5p/ROBO2 pathway at the post-transcriptional level. Single-cell analyses re-vealed that ROBO2 reduces the tumor-supportive role of cancer-associated fibroblasts (CAFs) by promoting programmed cell death of FAP/TGFB1 + CAFs, enhancing immune infiltration, and suppressing the TGF-β/Smad signaling pathway in fibroblasts and NSCLC cells. Finally, we con-firmed our findings through experiments, where OR7E47P directly binds to miR-183-5p, with a binding site that allows for endogenous competition, leading to the upregulation of ROBO2 ex-pression and potentially regulate TGF-β secretion of fibroblast, thereby regulating the TME in NSCLC.