Liu Jingjing, Cao Liming, Li Yuanyuan, Deng Pengbo, Pan Pinhua, Hu Chengping, Yang Huaping
Center of Respiratory Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Rd, Changsha, 410008, Hunan, China.
Hum Cell. 2022 Nov;35(6):1813-1823. doi: 10.1007/s13577-022-00766-6. Epub 2022 Aug 25.
Non-small cell lung cancer (NSCLC) is the malignancy with highest mortality and morbidity. Cancer-associated fibroblasts (CAFs) are the most abundant stromal cells in the tumor microenvironment of NSCLC. This research is performed to explore the biological functions of pirfenidone (PFD) to repress the malignant phenotypes of NSCLC cells, and its regulatory effects on exosomal microRNA-200 (exo-miR-200) derived from CAFs. In the present work, we report that, exo-miR-200 secreted by CAFs restrains the migration, invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells; PFD treatment promotes the secretion of exo-miR-200 from CAFs and enhances the tumor-suppressive properties of exo-miR-200 on NSCLC cells; zinc finger E-box binding homeobox 1 (ZEB1) is identified as a target of miR-200, and PFD treatment repressed the expression of ZEB1 in NSCLC cells via inducing the expression and secretion of miR-200 in CAFs. In conclusion, PFD-induced miR-200 overexpression in CAFs inhibits ZEB1 expression in NSCLC cells, and thus decelerates the migration, invasion and EMT process. Our study may provide clues for the treatment of NSCLC.
非小细胞肺癌（NSCLC）是死亡率和发病率最高的恶性肿瘤。癌症相关成纤维细胞（CAFs）是NSCLC肿瘤微环境中最丰富的基质细胞。本研究旨在探讨吡非尼酮（PFD）抑制NSCLC细胞恶性表型的生物学功能及其对CAFs来源的外泌体微小RNA-200（exo-miR-200）的调控作用。在本研究中，我们发现，CAFs分泌的exo-miR-200可抑制NSCLC细胞的迁移、侵袭和上皮-间质转化（EMT）；PFD处理可促进CAFs分泌exo-miR-200，并增强exo-miR-200对NSCLC细胞的肿瘤抑制特性；锌指E盒结合同源框1（ZEB1）被确定为miR-200的靶标，PFD处理通过诱导CAFs中miR-200的表达和分泌来抑制NSCLC细胞中ZEB1的表达。总之，PFD诱导CAFs中miR-200过表达可抑制NSCLC细胞中ZEB1的表达，从而减缓迁移、侵袭和EMT进程。我们的研究可能为NSCLC的治疗提供线索。
