• Keqi Liu, Xiaomin Li, Zhouzhou Yang, and Rong Zhang.
• Department of Thoracic Surgery, Sichuan Ya’an People’s Hospital, Ya’an City, China.
• Rev Invest Clin. 2022 Jan 1; 75 (2): 637563-75.

BackgroundCTHRC1 is highly expressed in various cancers.ObjectivesThe aim of the study was to study the role of CTHRC1 played in lung adenocarcinoma (LUAD) development and its underlying biological functions.MethodsEnriched pathways and upstream transcription factors of CTHRC1 were explored by bioinformatics analysis. Dual-luciferase assay and Chromatin immunoprecipitation assay were used to verify the binding relationship between CTHRC1 and HOXB9. CCK-8 was utilized to detect cell viability. Expression levels of CTHRC1, HOXB9, and angiogenesis-related genes were assessed by quantitative real time-polymerase chain reaction. Angiogenesis assay was used to detect angiogenesis ability. Quantitative analysis of metabolites were used to detect the accumulation of neutral lipids, the levels of free fatty acids (FAs), and glycerol. Western blot was conducted to measure expression of metabolic enzymes of FA.ResultsCTHRC1 was enriched in FA metabolic pathway, which was positively correlated and bound with HOXB9. CTHRC1 and HOXB9 expression was remarkably up-regulated in LUAD cells. Overexpression of CTHRC1 promoted FA metabolic pathway and angiogenesis, and FA inhibitor Orlistat restored it to NC group level. Meanwhile, CTHRC1 affected LUAD angiogenesis by activating HOXB9 to regulate FA metabolism.ConclusionsThis study found that activation of CTHRC1 by HOXB9 induces angiogenesis by mediating FA metabolism. CTHRC1 may be a potential target for LUAD diagnosis.Copyright: © 2022 Permanyer.

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