Elucidating the role of PBRM1 in NPC via RNA-seq transcriptomic sequencing

The PBRM1 (PB1) gene, which encodes BAF180, a specific subunit of the PBAF SWI / SNF complex, is extensively studied in some other cancers, yet its effects and related mechanisms in NPC remains inadequately understood. Aerobic glycolysis is one of the hallmarks of cancer, and whether PBRM1 is involved in this metabolic metastasis in NPC remains unclear.

We established NPC cell lines with knockdown of PBRM1 and performed functional analysis to understand the impact of their production. Based on the RNA-seq data, we mainly analyzed the activity of the AKT-mTOR signaling pathway and examined the expression levels of some key glycolytic genes including HIF 1α, PFKP, ENO 1, PKM and LDHA. Using in vivo experiments, we verified the effect of PBRM1 on the proliferation of NPC.

Our findings indicate that PBRM1 deficiency enhances proliferation, migration, and invasion in both CNE1 and CNE2 cells. Notably, PBRM1 downregulate activates the AKT-mTOR pathway, upregulating glycolytic enzymes and lactate production. Subcutaneous tumor formation assay in nude mice also showed that knockdown of PBRM1 promoted NPC cells growth.

This study illuminates PBRM1's tumor suppressor role, highlighting the AKT-mTOR pathway and aerobic glycolysis as potential therapeutic targets in NPC.