KDM4B/DHX9 promotes chemoresistance in small cell lung cancer through MYCN-Driven signaling pathway

Small cell lung cancer (SCLC) is prone to developing chemoresistance, which is associated with epigenetic reprogramming. While the involvement of LSD1-mediated histone demethylation has been reported, a systematic investigation into the role of the histone demethylase gene family in SCLC chemoresistance is lacking. In this study, we established nine chemoresistant cell lines from parental cells by gradually increasing drug concentrations and conducted RNA sequencing on these lines. Then, we performed linear regression and random effects meta-analysis on the RNA sequencing data to identify genes associated with chemoresistance among 23 demethylated proteins. Subsequently, we validated our findings using two neuroendocrine cell lines and their corresponding chemoresistant counterparts.