Huang Tonghai, Ren Kangqi, Ling Xiean, Li Zeyao, Chen Lin
Department of Thoracic Surgery, Shenzhen People's Hospital, 1st Affiliated Hospital of Southern University of Science and Technology, 2, Clinical Medical College of Jinan University, No.1017, East Gate Rd, Shenzhen, 518020, Guangdong, China.
Mol Cell Biochem. 2025 Mar;480(3):1831-1843. doi: 10.1007/s11010-024-05104-y. Epub 2024 Sep 11.
Non-small cell lung cancer (NSCLC) is a frequent type of lung cancer. Transcription factor Yin Yang 1 (YY1), an endogenous transcription factor containing zinc finger structure, can accelerate NSCLC progression. However, the impact of YY1 on the stemness of NSCLC cells and the mechanism of promoting NSCLC cell progression is unclear. YY1 and Sonic hedgehog (Shh) expressions were monitored by RT-qPCR, western blot, and immunohistochemistry. Overall survival was tested through Kaplan-Meier analysis. The interaction between YY1 and Shh was confirmed. Then, cell migration, stemness, and epithelial-mesenchymal transition (EMT) were assessed with functional experiments in vitro and in vivo. YY1 and Shh were highly expressed in NSCLC tissues and positively correlated with the poor OS of NSCLC patients. Functional experiments denoted that YY1 or Shh overexpression could accelerate EMT, migration, and stemness of NSCLC cells, and YY1 or Shh knockdown played the opposite role to its overexpression. Mechanism analysis disclosed that Shh, as a target gene of YY1, was positively related to YY1. The rescued experiment manifested that Shh silencing could reverse the induction effect of YY1 overexpression on EMT, migration, and stemness of NSCLC cells. In vivo experiments also confirmed that YY1 could accelerate tumor growth and EMT and weaken apoptosis. YY1 promotes NSCLC EMT, migration, and stemness by Shh, which might be novel diagnostic markers and therapeutic targets for NSCLC therapy.
非小细胞肺癌（NSCLC）是一种常见的肺癌类型。转录因子阴阳1（YY1）是一种含锌指结构的内源性转录因子，可加速NSCLC进展。然而，YY1对NSCLC细胞干性的影响以及促进NSCLC细胞进展的机制尚不清楚。通过RT-qPCR、蛋白质免疫印迹和免疫组织化学监测YY1和音猬因子（Shh）的表达。通过Kaplan-Meier分析测试总生存期。证实了YY1与Shh之间的相互作用。然后，通过体外和体内功能实验评估细胞迁移、干性和上皮-间质转化（EMT）。YY1和Shh在NSCLC组织中高表达，且与NSCLC患者的不良总生存期呈正相关。功能实验表明，YY1或Shh过表达可加速NSCLC细胞的EMT、迁移和干性，而YY1或Shh基因敲低则发挥与其过表达相反的作用。机制分析显示，Shh作为YY1的靶基因，与YY1呈正相关。挽救实验表明，Shh沉默可逆转YY1过表达对NSCLC细胞EMT、迁移和干性的诱导作用。体内实验也证实，YY1可加速肿瘤生长和EMT并减弱细胞凋亡。YY1通过Shh促进NSCLC的EMT、迁移和干性，这可能是NSCLC治疗的新型诊断标志物和治疗靶点。
