Research progress on the regulatory mechanisms of FOXC1 expression in cancers and its role in drug resistance

Yang, Yihui; Li, Wan; Yang, Hong; Zhang, Yizhi; Zhang, Sen; Xu, Fang; Hao, Yue; Cao, Wanxin; Du, Guanhua; Wang, Jinhua

doi:10.1016/j.gene.2023.148079

Gene

2024

DOI: 10.1016/j.gene.2023.148079

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Research progress on the regulatory mechanisms of FOXC1 expression in cancers and its role in drug resistance

Yihui Yang,

Wan Li,

Hong Yang

et al.

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2024

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FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway

Li,

Chen,

Xiao

et al. 2024

Cell Biol Toxicol

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Background 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. Methods 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. Results 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. Conclusion 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.

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FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway

Li,

Chen,

Xiao

et al. 2024

Cell Biol Toxicol

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show abstract

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Research progress on the regulatory mechanisms of FOXC1 expression in cancers and its role in drug resistance

Cited by 1 publication

References 101 publications

FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway

FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway

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