Guan Xiaojiao, Liang Jie, Xiang Yifan, Li Tian, Zhong Xinwen
Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang 110001, China.
Int J Biol Macromol. 2024 Mar;261(Pt 2):129717. doi: 10.1016/j.ijbiomac.2024.129717. Epub 2024 Jan 28.
Underlying molecular mechanisms of BARX homeobox 1 (BARX1) in lung adenocarcinoma (LUAD) remain elusive.
Abnormally expressed genes in LUAD tissues were analyzed by RNA-sequencing. CCK-8, colony formation, transwell, and wound healing assays examined proliferation, colony formation, invasion, and migration of LUAD cells, respectively. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay examined the interaction between BARX1 and Forkhead Box F1 (FOXF1). Xenograft mouse model of LUAD was constructed to monitor the growth and metastasis of tumor.
BARX1 was upregulated, FOXF1 was downregulated in LUAD tissues and cells. There was a negative correlation between BARX1 and FOXF1 expression. BARX1 deficiency limited malignant phenotypes of LUAD cells, including proliferation, invasion, migration and EMT. In vivo, BARX1 knockdown suppressed tumor growth and metastasis in A549-drove xenograft mouse model. BARX1 interacted with FOXF1 promoter and repressed FOXF1 expression. Upregulation of BARX1 promoted the expression of Wnt5a, β-catenin, and phosphorylated-glycogen synthase kinase-3 beta (p-GSK3β), whereas inhibited FOXF1, p-β-catenin, and GSK3β in LUAD cells. BARX1 knockdown caused an opposite result. Rescue assays uncovered that FOXF1 reversed the impact of BARX1 on malignant phenotypes and Wnt/β-catenin of LUAD cells.
BARX1 repressed FOXF1 expression and activated Wnt/β-catenin signaling pathway to drive lung adenocarcinoma.
BARX同源盒1（BARX1）在肺腺癌（LUAD）中的潜在分子机制仍不清楚。
通过RNA测序分析LUAD组织中异常表达的基因。CCK-8、集落形成、Transwell和伤口愈合试验分别检测LUAD细胞的增殖、集落形成、侵袭和迁移。电泳迁移率变动分析和染色质免疫沉淀试验检测BARX1与叉头框F1（FOXF1）之间的相互作用。构建LUAD的异种移植小鼠模型以监测肿瘤的生长和转移。
BARX1在LUAD组织和细胞中上调，FOXF1下调。BARX1与FOXF1表达之间存在负相关。BARX1缺陷限制了LUAD细胞的恶性表型，包括增殖、侵袭、迁移和上皮-间质转化。在体内，BARX1基因敲低抑制了A549驱动的异种移植小鼠模型中的肿瘤生长和转移。BARX1与FOXF1启动子相互作用并抑制FOXF1表达。BARX1的上调促进了LUAD细胞中Wnt5a、β-连环蛋白和磷酸化糖原合酶激酶-3β（p-GSK3β）的表达，而抑制了FOXF1、p-β-连环蛋白和GSK3β。BARX1基因敲低导致相反的结果。挽救试验发现，FOXF1逆转了BARX1对LUAD细胞恶性表型和Wnt/β-连环蛋白的影响。
BARX1抑制FOXF1表达并激活Wnt/β-连环蛋白信号通路以驱动肺腺癌。
