FOXC1 转录抑制 ABHD5,通过 AMPK/mTOR 通路抑制肾细胞癌的进展。
FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway.
发表日期:2024 Aug 02
作者:
Jianfa Li, Shuangchen Chen, Jing Xiao, Jiayuan Ji, Chenchen Huang, Ge Shu
来源:
CELL BIOLOGY AND TOXICOLOGY
摘要:
转录因子 FOXC1 活性的增加导致靶基因的转录增加,最终促进各种癌症类型的进展。但目前尚无FOXC1在肾细胞癌中作用的文献报道。通过RT-qPCR、免疫组化和Western blotting等方法评估FOXC1 mRNA和蛋白的表达。利用功能获得实验来评估细胞的增殖和转移能力。建立裸鼠模型用于移植肿瘤并建立肺转移模型以观察细胞在活体中的增殖和扩散。利用生物分析、CHIP测定、荧光素酶测定、RT-qRCR和蛋白质印迹实验等多种技术来研究FOXC1如何在分子水平上促进ABHD5的转录。通过Western blot评估FOXC1对AMPK/mTOR信号通路的影响。FOXC1在RCC中表达下调,导致RCC患者预后不良。进一步的实验表明,强制FOXC1表达可显着抑制RCC细胞的生长和细胞转移。机械上,FOXC1促进ABHD5的转录,激活AMPK信号通路,抑制mTOR信号通路。最后,ABHD5的敲低恢复了FOXC1过表达诱导的细胞生长和转移抑制的抑制作用。总的来说,我们的研究表明FOXC1通过促进ABHD5转录调节AMPK/mTOR信号通路发挥其抑癌作用。 FOXC1 既可以作为 RCC 的诊断指标,也可以作为潜在的治疗重点。© 2024。作者。
Increased activity of the transcription factor FOXC1 leads to elevated transcription of target genes, ultimately facilitating the progression of various cancer types. However, there are currently no literature reports on the role of FOXC1 in renal cell carcinoma.By using RT-qPCR, immunohistochemistry and Western blotting, FOXC1 mRNA and protein expression was evaluated. Gain of function experiments were utilized to assess the proliferation and metastasis ability of cells. A nude mouse model was created for transplanting tumors and establishing a lung metastasis model to observe cell proliferation and spread in a living organism. Various techniques including biological analysis, CHIP assay, luciferase assay, RT-qRCR and Western blotting experiments were utilized to investigate how FOXC1 contributes to the transcription of ABHD5 on a molecular level. FOXC1 was assessed by Western blot for its impact on AMPK/mTOR signaling pathway.FOXC1 is down-regulated in RCC, causing unfavorable prognosis of patients with RCC. Further experiments showed that forced FOXC1 expression significantly restrains RCC cell growth and cell metastasis. Mechanically, FOXC1 promotes the transcription of ABHD5 to activate AMPK signal pathway to inhibit mTOR signal pathway. Finally, knockdown of ABHD5 recovered the inhibitory role of FOXC1 overexpression induced cell growth and metastasis suppression.In general, our study demonstrates that FOXC1 exerts its tumor suppressor role by promoting ABHD5 transcription to regulating AMPK/mTOR signal pathway. FOXC1 could serve as both a diagnostic indicator and potential treatment focus for RCC.© 2024. The Author(s).