title: B7-H3 regulates lipid metabolism of lung cancer through SREBP1-mediated expression of FASN.
abstract: B7-H3 is a glycoprotein overexpressed in cancer, but its functional contribution in this setting remains poorly understood. In the present study, we identified that the overexpression of B7-H3 in lung cancer resulted in aberrant lipid metabolism via SREBP-1/FASN signaling pathway. Immunohistochemical analysis of tissue microarrays revealed that approximately 80.4% (37/46) of lung cancer tissues were positive for B7-H3 accompanying poor prognosis. Notably, Oil red O staining and total triglyceride assay exhibited that down-regulation of B7-H3 decreased lipid synthesis in lung cancer A549 and H446 cell lines. Mechanistic investigations showed that B7-H3 modulated the expression of FASN, a fatty acid synthase, specifically. Furthermore, deletion of B7-H3 down-regulated the mRNA and protein levels of SREBP-1, a transcription factor governing the expression of FASN. Finally, correlation analysis between expression levels of B7-H3 and FASN exhibited a positive correlation in clinical lung cancer tissues. Overall, we conclude that B7-H3 hijacks SREBP-1/FASN signaling mediating abnormal lipid metabolism in lung cancer. Our finding provides new insights into the function and mechanism of B7-H3 in the development of lung cancer.
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, PR China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, PR China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Dong
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, PR China.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Feng
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, PR China. Electronic address: cuiming0403@bjmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Cui
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, PR China. Electronic address: fansaijun@irm-cams.ac.cn.
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
mesh_terms: D000072283:A549 Cells; D060887:B7 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D046888:Tissue Array Analysis; D014280:Triglycerides / Q000737:chemistry
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I
keywords: Abnormal lipid metabolism; B7-H3; FASN; Lung cancer; SREBP1