ILF3 mediates lipid metabolism to promote pancreatic cancer development by regulating CPT1A-activated PPARa signaling pathway.

Interleukin enhancer binding factor 3 (ILF3) serves as a coactivator for transcription and has been associated with the growth and spread of tumors, despite its unclear involvement in pancreatic cancer (PC). To elucidate the significance of ILF3 in PC, we examined its expression levels at both the tissue and cellular levels. Additionally, we investigated its biological functions and underlying mechanisms using PANC-1 and MIAPaCa-2 cell lines. Our findings indicate that ILF3 expression is elevated in both PC clinical samples and cell lines when compared to normal samples. Moreover, in vitro and in vivo experiments demonstrated that silencing ILF3 hindered tumor growth, attenuated anti-apoptotic capacity, and reduced lipid accumulation. According to our RNA immunoprecipitation-sequencing (RIP-seq) analysis, ILF3 was found to bind to specific targets. To gain a better understanding of ILF3's functions, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Mechanistically, we discovered that the ILF3 protein interacts with the carnitine palmitoyltransferase 1A (CPT1A) gene. Silencing ILF3 is essential in inhibiting PC development, as it elevates peroxisome proliferators-activated receptor α (PPARα) levels through augmented CPT1A expression. Consequently, lipid accumulation is diminished. In conclusion, our research has revealed a novel role for ILF3 in controlling lipid metabolism, specifically through its interaction with CPT1A mRNA in the PPARα signaling pathway. This discovery offers a conceptual basis for further exploring the pathological mechanism of PC.