MED23 depletion induces premature senescence in NSCLC cells by interacting with BCLAF1 and then suppressing NUPR1 expression

Abstract

Lung cancer is the leading cause of cancer death worldwide. 85 % of lung cancers are categorized by their histological types as a non-small cell lung cancer (NSCLC) subtype. While the MED23 subunit of the mediator complex has been implicated in lung cancer development, the precise underlying mechanism remains unclear. Our research indicates that elevated MED23 expression is linked to reduced overall survival rates in NSCLC. Depletion of MED23 triggers premature senescence in NSCLC cells. Furthermore, through co-IP and mass spectrometry analyses, we have identified BCLAF1 as a binding partner of MED23, with subsequent confirmation via PLA assays. Subsequently, NUPR1, a transcriptional cofactor known to induce premature senescence in lung cancer cells by disrupting autophagic processes, was validated as a downstream target of the MED23/BCLAF1 complex through RNA-seq and ChIP assays. Thus, the interaction between MED23 and BCLAF1 regulates NUPR1 expression, impacting autophagic flux and leading to premature senescence in NSCLC cells.

Keywords: BCLAF1; MED23; NSCLC; NUPR1; Premature senescence.