Lactate activates CCL18 expression via H3K18 lactylation in macrophages to promote tumorigenesis of ovarian cancer  

作　　者：Jinrui Sun Qinmei Feng Yue He Ming Wang Yumei Wu 

机构地区：[1]Department of Gynecology,Shanxi Provincial People’s Hospital,Taiyuan 030001,China [2]Department of Gynecologic Oncology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital,Beijing 100006,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第9期1373-1386,共14页生物化学与生物物理学报（英文版）

摘　　要：This study investigates the role of lactate in the genesis and progression of ovarian cancer(OV)and explores the underlying mechanisms.Serum lactate levels show a positive correlation with tumor grade and poor prognosis in patients with OV.Bioinformatics analysis identifies CCL18 as a lactate-related gene in OV.CCL18 is up-regulated in cancerous tissues and positively related to serum lactate levels in OV patients.THP-1 cells are exposed to phorbol-12-myristate-13-acetate for M0 macrophage induction.The results of RT-qPCR and ELISA for M1/M2 macrophage-related markers and inflammatory cytokines show that the exposure of lactate to macrophages induces M2 polarization.Based on the coculture of OV cells with macrophages,lactate-treated macrophages induces a significant increase in the proliferation and migration of OV cells.However,these effects can be reversed by silencing of Gpr132 in macrophages or treatment with anti-CCL18 antibody.Experiments using the xenograft model verify that the oncogenic role of lactate in tumor growth and metastasis relies on Gpr132 and CCL18.ChIP-qPCR and luciferase reporter assays reveal that lactate regulates CCL18 expression via H3K18 lactylation.In conclusion,lactate is a potential therapeutic target for OV.It is involved in tumorigenesis by activating CCL18 expression via H3K18 lactylation in macrophages.

关 键 词：ovarian cancer LACTATE MACROPHAGE CCL18 lactylation 

分 类 号：R737.31[医药卫生—肿瘤]