Novel transcription factor BTNL9 enhances tumor suppression and drug sensitivity in non-small cell lung cancer through cell cycle regulation [RNA-seq]

Here, we identify BTNL9 as a non-canonical transcriptional regulator and investigate its function in non-small cell lung cancer (NSCLC). Coiled-coil prediction, native PAGE, and co-immunoprecipitation demonstrated BTNL9 homodimerization via its bZIP-like region, while subcellular fractionation and immunofluorescence confirmed its presence in both the nucleus and cytoplasm.

Chromatin immunoprecipitation sequencing (ChIP-seq) analysis identified 9709 BTNL9-associated genomic regions, including sites proximal to transcription start sites, with enrichment of a cytosine-rich motif. Whether chromatin association reflects direct DNA binding or indirect co-regulatory interaction remains to be experimentally confirmed. Integrated transcriptomic and protein analyses revealed that BTNL9 overexpression represses genes involved in cell cycle progression and DNA replication while activating a subset of p53-associated pathways.