Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China.
Cancer Sci. 2023 Sep;114(9):3568-3582. doi: 10.1111/cas.15884. Epub 2023 Jun 13.
BACH1 plays an important role in promoting cancer. This study aims to further verify the relationship between the expression level of BACH1 in lung adenocarcinoma prognosis, as well as the influence of BACH1 expression on lung adenocarcinoma and the potential mechanism. The expression level of BACH1 in lung adenocarcinoma and its relationship with prognosis was evaluated by lung adenocarcinoma tissue microarray analysis combined with bioinformatics approaches. Gene knockdown and overexpression were used to investigate the functions and molecular mechanisms of BACH1 in lung adenocarcinoma cells. The regulatory downstream pathways and target genes of BACH1 in lung adenocarcinoma cells were explored by bioinformatics and RNA sequencing data analysis, real-time PCR, western blot analysis, and cell immunofluorescence and cell adhesion assays. Chromatin immunoprecipitation and dual-luciferase reporter assays were carried out to verify the target gene binding site. In the present study, BACH1 is abnormally highly expressed in lung adenocarcinoma tissues, and high BACH1 expression is negatively correlated with patient prognosis. BACH1 promotes the migration and invasion of lung adenocarcinoma cells. Mechanistically, BACH1 directly binds to the upstream sequence of the ITGA2 promoter to promote ITGA2 expression, and the BACH1-ITGA2 axis is involved in cytoskeletal regulation in lung adenocarcinoma cells by activating the FAK-RAC1-PAK signaling pathway. Our results indicated that BACH1 positively regulates the expression of ITGA2 through a transcriptional mechanism, thereby activating the FAK-RAC1-PAK signaling pathway to participate in the formation of the cytoskeleton in tumor cells and then promoting the migration and invasion of tumor cells.
BACH1 在促进癌症方面发挥着重要作用。本研究旨在进一步验证 BACH1 在肺腺癌预后中的表达水平与肺腺癌的关系，以及 BACH1 表达对肺腺癌的影响及其潜在机制。通过肺腺癌组织微阵列分析结合生物信息学方法评估 BACH1 在肺腺癌中的表达水平及其与预后的关系。利用基因敲低和过表达技术研究 BACH1 在肺腺癌细胞中的功能和分子机制。通过生物信息学和 RNA 测序数据分析、实时 PCR、Western blot 分析、细胞免疫荧光和细胞黏附实验，探讨 BACH1 在肺腺癌细胞中的下游调控途径和靶基因。通过染色质免疫沉淀和双荧光素酶报告基因实验验证靶基因结合位点。本研究表明，BACH1 在肺腺癌组织中异常高表达，且高 BACH1 表达与患者预后呈负相关。BACH1 促进肺腺癌细胞的迁移和侵袭。机制上，BACH1 可直接结合 ITGA2 启动子的上游序列，促进 ITGA2 的表达，BACH1-ITGA2 轴通过激活 FAK-RAC1-PAK 信号通路参与肺腺癌细胞骨架的调节。我们的结果表明，BACH1 通过转录机制正向调节 ITGA2 的表达，从而激活 FAK-RAC1-PAK 信号通路，参与肿瘤细胞骨架的形成，进而促进肿瘤细胞的迁移和侵袭。
