Wang Xiaohua, Qu Xinjuan, Liu Xuelai, Wang Kaiyue, Yang Yongfang, Zhang Yujuan, Wang Zhenguo, Fan Guangjian, Li Yuming, Zeng Yuanyuan, Chen Hongwei, Zhu Ting
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510006, China.
Department of General Internal Medicine, Linyi People's Hospital, No.27 Jiefang Road, Lanshan District, Linyi City, Shandong Province, 276003, China.
Biochem Biophys Rep. 2024 Nov 27;41:101885. doi: 10.1016/j.bbrep.2024.101885. eCollection 2025 Mar.
Glioma, the most frequent central nervous system malignancy, is often promoted by the overexpression of Fos-like antigen 1 (FOSL1). However, the regulation of FOSL1 remains unexplored. The present study aimed to investigate the regulatory mechanism of FOSL1 to identify potential therapeutic targets for glioblastoma.
This study's initial investigation utilized dual-luciferase reporter gene assays and quantitative polymerase chain reaction (qPCR) assays to establish that Kruppel-like factor 14 (KLF14) inhibits the transcription of FOSL1. Subsequent immunohistochemistry and western blotting (WB) assays on glioma tissues confirmed a negative association between FOSL1 and KLF14. This study generated KLF14 knockdown cells and double knockdown cells of KLF14 and FOSL1 and further assessed cell growth through various experimental methods. The impact of KLF14 on tumor cell migration via FOSL1 was determined using qPCR and WB assays. A xenograft tumor model was utilized to verify tumor growth suppression by KLF14.
The present study demonstrated that KLF14 restrains FOSL1 transcription and is inversely correlated with FOSL1 in glioma tissues. KLF14 overexpression was found to counteract FOSL1's effect on cell migration and epithelial-to-mesenchymal transition in glioma cells, which coincided with decreased Snail2 and cluster of differentiation 44 (CD44) expressions. Further, KLF14 overexpression was shown to hinder tumor progression in vivo.
This study highlights that FOSL1 is negatively regulated by KLF14 in glioblastoma and suggests that KLF14 overexpression can mitigate tumor growth by inhibiting FOSL1, thus identifying KLF14 as a novel molecular target for treating glioblastoma. Further research into the interplay and regulatory dynamics between KLF14 and FOSL1 under varying stress conditions can enhance the precision of glioblastoma treatment.
胶质瘤是最常见的中枢神经系统恶性肿瘤，通常由Fos样抗原1（FOSL1）的过表达所促进。然而，FOSL1的调控机制仍未得到探索。本研究旨在探究FOSL1的调控机制，以确定胶质母细胞瘤的潜在治疗靶点。
本研究首先利用双荧光素酶报告基因测定法和定量聚合酶链反应（qPCR）测定法确定Kruppel样因子14（KLF14）抑制FOSL1的转录。随后对胶质瘤组织进行免疫组织化学和蛋白质印迹（WB）测定，证实FOSL1与KLF14之间呈负相关。本研究构建了KLF14敲低细胞以及KLF14和FOSL1的双敲低细胞，并通过各种实验方法进一步评估细胞生长情况。使用qPCR和WB测定法确定KLF14通过FOSL1对肿瘤细胞迁移的影响。利用异种移植肿瘤模型验证KLF14对肿瘤生长的抑制作用。
本研究表明，KLF14抑制FOSL1转录，且在胶质瘤组织中与FOSL1呈负相关。发现KLF14过表达可抵消FOSL1对胶质瘤细胞迁移和上皮-间质转化的影响，这与Snail2和分化簇44（CD44）表达降低相一致。此外，KLF14过表达在体内可阻碍肿瘤进展。
本研究强调在胶质母细胞瘤中FOSL1受KLF14负调控，并表明KLF14过表达可通过抑制FOSL1减轻肿瘤生长，从而确定KLF14为治疗胶质母细胞瘤的新型分子靶点。进一步研究KLF14与FOSL1在不同应激条件下的相互作用和调控动态，可提高胶质母细胞瘤治疗的精准性。
