Abstract
The transcription factor PBX1 is regarded as an oncogene in various cancers, but its role in non-small cell lung cancer (NSCLC) and the detailed mechanism is not known. In the present study, we found that PBX1 is downregulated in NSCLC tissues and inhibits NSCLC cell proliferation and migration. Subsequently, we performed an affinity purification-coupled tandem mass spectrometry (MS/MS) and found the ubiquitin ligase TRIM26 in the PBX1 immunoprecipitates. Moreover, TRIM26 binds to and mediates PBX1 for K48-linked polyubiquitination and proteasomal degradation. Noticeably, TRIM26 activity depends on its C-terminal RING domain when it is deleted TRIM26 loses its function towards PBX1. TRIM26 further inhibits PBX1 transcriptional activity and downregulates the PBX1 downstream genes, such as RNF6. Moreover, we found that overexpression of TRIM26 significantly promotes NSCLC proliferation, colony formation, and migration in contradiction to PBX1. TRIM26 is highly expressed in NSCLC tissues and predicts poor prognosis. Lastly, the growth NSCLC xenografts is promoted by overexpression of TRIM26 but is suppressed by TRIM26 knockout. In conclusion, TRIM26 is a ubiquitin ligase of PBX1 and it promotes while PBX1 inhibits NSCLC tumor growth. TRIM26 might be a novel therapeutic target for the treatment of NSCLC.