UNASSIGNED: The aim of the study was to study the role of CTHRC1 played in lung adenocarcinoma (LUAD) development and its underlying biological functions.
UNASSIGNED: Enriched 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.
UNASSIGNED: CTHRC1 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.
UNASSIGNED: This study found that activation of CTHRC1 by HOXB9 induces angiogenesis by mediating FA metabolism. CTHRC1 may be a potential target for LUAD diagnosis.
■该研究的目的是研究CTHRC1在肺腺癌(LUAD)发展中的作用及其潜在的生物学功能。
■通过生物信息学分析探索了CTHRC1的富集途径和上游转录因子。使用双荧光素酶测定和染色质免疫沉淀测定来验证CTHRC1与HOXB9之间的结合关系。CCK-8用于检测细胞活力。通过定量实时聚合酶链反应评估CTHRC1,HOXB9和血管生成相关基因的表达水平。血管生成试验用于检测血管生成能力。代谢物的定量分析用于检测中性脂质的积累,游离脂肪酸(FAs)的水平,和甘油。进行蛋白质印迹以测量FA的代谢酶的表达。
■CTHRC1在FA代谢途径中富集,与HOXB9呈正相关并结合。在LUAD细胞中CTHRC1和HOXB9表达显著上调。CTHRC1过表达促进FA代谢途径和血管生成,FA抑制剂奥利司他将其恢复至NC组水平。同时,CTHRC1通过激活HOXB9调节FA代谢影响LUAD血管生成。
■这项研究发现,HOXB9激活CTHRC1通过介导FA代谢诱导血管生成。CTHRC1可能是诊断LUAD的潜在靶点。