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. 2026 Feb 21.
doi: 10.1007/s12672-026-04682-1. Online ahead of print.

USP14 promotes epithelial-mesenchymal transition and functions as a multifaceted biomarker in lung adenocarcinoma

Chenzhuo Wu #  1   2   3 , Zhimeng Chen #  1   2   3 , Jian Yang #  1   2   3 , Hao Shi  4 , Yuxuan Xing  1   2   3 , Haoran Liu  1   2   3 , Ziqing Shen  1   2   3 , Chun Xu  1   2   3 , Cheng Ding  1   2   3 , Hao Ding  5   6   7 , Jun Zhao  8   9   10
Affiliations

USP14 promotes epithelial-mesenchymal transition and functions as a multifaceted biomarker in lung adenocarcinoma

Chenzhuo Wu et al. Discov Oncol. .

Abstract

Ubiquitin-specific protease 14 (USP14) is highly expressed in various tumors and functions as a critical regulator of proteasomal protein degradation. However, a comprehensive understanding of clinical relevance, prognostic value, and immunotherapy prediction of USP14 in lung adenocarcinoma (LUAD) has yet to be established. USP14 expression was found upregulated and related with poor survival in LUAD using transcriptome and proteome data from TCGA and PDC databases. Then functional and rescue experiments showed that USP14 increases the ability of LUAD cells to migrate, invade, and undergo epithelial-mesenchymal transition (EMT) through Wound-healing assays, Transwell assays and western blot. Furthermore, enrichment analysis positioned USP14 as a positive regulator of the PI3K-AKT-mTOR signaling pathway. Moreover, immune cell infiltration analysis in relation to USP14 expression reveals its association with immune evasion and low response of immunotherapy. In conclusion, USP14 contributes to LUAD development through three key mechanisms: suppressing immune responses, promoting EMT, and activating the Akt signaling pathway. Our research establishes USP14 as a multifaceted biomarker and immunotherapy target. These findings provide a deeper understanding of USP14's crucial role in LUAD.

Keywords: AKT; EMT; Immunotherapy; Lung adenocarcinoma; USP14.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All methods were carried out in accordance with the Declaration of Helsinki. Ethical approval was not required as the study used only secondary data from publicly available, de-identified sources. All utilized public data sets were generated by others who obtained ethical approval. Competing interests: The authors declare no competing interests.

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