title: Estrogen suppresses hepatocellular carcinoma cells through ERβ-mediated upregulation of the NLRP3 inflammasome.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The incidence of HCC is strikingly higher in males than in females. The remarkable gender disparity suggests an important role for sex hormones in HCC pathogenesis. Recently, estrogen has emerged as a protective factor in the development and progression of HCC, but whether it prevents and attenuates HCC, and the mechanism of protection, have not been elucidated. The present study shows that expression of estrogen receptor (ER) β was significantly downregulated in HCC tissue compared with normal liver tissue; moreover, its expression level showed a significant negative correlation with disease progression and a positive correlation with the expression level of NLRP3 inflammasome components. In a previous study, we showed that loss of NLRP3 inflammasome in HCC tissue contributed to tumor progression, whereas the mechanism of its deregulation was not elucidated. In this study, we investigated the potential link between NLRP3 inflammasome and estrogen. Our data reveal that treatment with 17β-estradiol (E2) significantly inhibited the malignant behavior of HCC cells through E2/ERβ/MAPK pathway-mediated upregulation of the NLRP3 inflammasome. This study shows a novel link between ERβ and the NLRP3 inflammasome in HCC progression, which provides a potentially valuable therapeutic strategy for treatment of HCC patients.
authors.affiliation: 1] Department of Immunology, Shandong University School of Medicine, Jinan, China [2] Medical Laboratory Diagnosis Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Mu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Wanwan
authors.initials: W
authors.lastname: Huai
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004958:Estradiol / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D002352:Carrier Proteins; D047629:Estrogen Receptor beta; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D004958:Estradiol