H3k18la Regulates Ccr7 In Caf To Promote Oscc

The elevated lactate level in oral squamous cell carcinoma (OSCC) may affect the tumor microenvironment (TME) through lactylation, but the specific mechanism is still unknown. Our previous study has shown that CCR7 in the TME promotes the proliferation and migration of OSCC. This study focuses on the effect of lactylation on cancer-associated fibroblasts (CAF) through CCR7. We established a mouse model of OSCC lymph node metastasis and investigated the effect of lactate on OSCC through IHC experiments and GEO database analysis by lactylation. We constructed a CCR7 knockout mouse model and analyzed the effect of CCR7 on OSCC in the TME with the support of scRNA-seq. Through mouse OSCC experiments, Western blot, ChIP-seq, ChIP-qPCR, Rt-qPCR, CCK-8, wound healing assays, and Transwell assays, we demonstrated that lactate regulates CCR7 expression through H3K18 lactylation, thereby influencing OSCC. 1. Through in vivo experiment, we found that lactate promotes the proliferation and migration of OCSS and affects the Pan-Kla and H3K18la levels in the TME. 2. By utilizing scRNA-seq, we discovered that CCR7 knockout markedly influences the function of CAF within the TME. 3. Through further cell experiments on CAF, we proved that lactate promotes the transcription of CCR7 by lactylation at the H3K18 site and opening the CCR7 promoter region, thereby promoting the proliferation and migration of OSCC. In CAF, lactate induces H3K18la on the promoter region of CCR7, opening specific sites and mediating CCR7 transcription, thereby promoting the proliferation and migration of OSCC.