Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
Suzhou Key Laboratory for Respiratory Diseases, Suzhou, China.
Cancer Med. 2023 Apr;12(8):9826-9842. doi: 10.1002/cam4.5746. Epub 2023 Feb 27.
Forkhead box L2 (FOXL2) has been recognized as a transcription factor in the progression of many malignancies, but its role in non-small cell lung cancer (NSCLC) remains unclear. This research clarified on the role of FOXL2 and the specific molecular mechanism in NSCLC.
RNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting assays. Cell proliferation was examined by cell counting kit-8 (CCK-8) and clonogenic assays. Transwell and wound healing assays were used to detect cell invasion and migration. Cell cycle alterations were assessed by flow cytometry. The relationship between FOXL2 and miR-133b was verified by dual-luciferase reporter assays. In vivo metastasis was monitored in the tail vein-injected mice.
FOXL2 was upregulated in NSCLC cells and tissues. Downregulation of FOXL2 restrained cell proliferation, migration, and invasion and arrested the cell cycle of NSCLC cells. Moreover, FOXL2 promoted the epithelial-mesenchymal transition (EMT) process of NSCLC cells by inducing the transforming growth factor-β (TGF-β)/Smad signaling pathway. miR-133b directly targeted the 3'-UTR of FOXL2 and negatively regulated FOXL2 expression. Knockdown of FOXL2 blocked metastasis in vivo.
miR-133b downregulates FOXL2 by targeting the 3'-UTR of FOXL2, thereby inhibiting cell proliferation, EMT and metastasis induced by the TGF-β/Smad signaling pathway in NSCLC. FOXL2 may be a potential molecular target for treating NSCLC.
叉头框 L2（FOXL2）已被认为是许多恶性肿瘤进展中的转录因子，但它在非小细胞肺癌（NSCLC）中的作用尚不清楚。本研究阐明了 FOXL2 在 NSCLC 中的作用及其具体分子机制。
通过实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测 RNA 和蛋白质水平。通过细胞计数试剂盒-8（CCK-8）和集落形成测定法检测细胞增殖。通过 Transwell 和划痕愈合测定法检测细胞侵袭和迁移。通过流式细胞术评估细胞周期变化。通过双荧光素酶报告基因测定验证 FOXL2 和 miR-133b 之间的关系。通过尾静脉注射小鼠监测体内转移。
FOXL2 在 NSCLC 细胞和组织中上调。FOXL2 的下调抑制了 NSCLC 细胞的增殖、迁移和侵袭，并阻滞了细胞周期。此外，FOXL2 通过诱导转化生长因子-β（TGF-β）/Smad 信号通路促进 NSCLC 细胞的上皮-间充质转化（EMT）过程。miR-133b 直接靶向 FOXL2 的 3'-UTR，并负调控 FOXL2 的表达。FOXL2 的敲低阻断了体内转移。
miR-133b 通过靶向 FOXL2 的 3'-UTR 下调 FOXL2，从而抑制 TGF-β/Smad 信号通路诱导的 NSCLC 细胞增殖、EMT 和转移。FOXL2 可能是治疗 NSCLC 的潜在分子靶点。
