USP28-mediated deubiquitination of FOXK1 activates the Hippo signaling pathway to regulate cell proliferation and radiosensitivity in lung cancer

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-02-19 DOI:10.1016/j.lfs.2025.123483

Yimei Meng , Yunhong Xu , Anchen Qiu , Ming Lin , Liu Yang , Yumei Huang

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引用次数: 0

Abstract

Aims

Radioresistance remains a significant challenge for lung cancer therapeutics. Forkhead box K1 (FOXK1) plays a role in regulating various biological processes and the progression of multiple cancers. However, the role of FOXK1 in lung cancer progression and radioresistance are not fully understood.

Main methods

Functional analyses were conducted on lung cancer cells transfected with specified siRNAs or plasmids. The ubiquitination of FOXK1 was evaluated by in vitro ubiquitination assays. RNA sequencing analysis was conducted to identify the downstream signaling pathway regulated by FOXK1. Mouse xenograft models were constructed using lung cancer cells with stable expression of either sh-NC or sh-FOXK1. Immunohistochemistry was used to assess FOXK1 and USP28 expression levels in lung cancer and paired normal lung tissues.

Key findings

We found that elevated FOXK1 expression markedly enhances radioresistance and tumorigenesis in lung cancer. Furthermore, we demonstrated that ubiquitin specific peptidase 28 (USP28) interacts with and targets FOXK1 for deubiquitination and stabilization. Moreover, we showed that FOXK1 exerts its biological function via activating the Hippo pathway.

Significance

Our research showed that FOXK1 is deubiquitinated by USP28 and facilitates cell proloferation and radioresistance by activating the Hippo pathway, suggesting that FOXK1 may act as a potential radiosensitizing target for lung cancer.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.