Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer - Article

Sep 22, 2026

Ubiquitin-Activating Enzyme E1 (UBA1) is an E1 enzyme that activates ubiquitin-conjugating enzymes, and its role in breast cancer (BC) had remained insufficiently defined. Using mRNA sequencing analysis of BC patients, the study finds UBA1 mRNA markedly elevated in tumor tissues versus controls, with high UBA1 expression associated with poorer overall survival, disease-specific survival, and progression-free survival. UBA1 is proposed as an independent prognostic and diagnostic biomarker. Functional enrichment links UBA1 to inflammation-related pathways, including TNF-α and IL-6 signaling, and immune-associated processes, while ssGSEA indicates a negative association between UBA1 and multiple infiltrating immune cell types. Silencing UBA1 suppresses BC cell line growth, supporting its therapeutic potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Abstract

Introduction

Breast cancer burden and heterogeneity

Advances in diagnosis and treatment

Need for new biomarkers and therapeutic targets

Ubiquitination and cancer biology

Article Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications Mingtao Feng 1,2,†, Huanhuan Cui 1,2,†, Sen Li 1,2, Liangdong Li 1,2, Changshuai Zhou 1,2, Lei Chen 1,2, Yiqun Cao 1,2, Yang Gao 1,2,* and Deheng Li 1,2, * Citation: Feng, M.; Cui, H.; Li, S.; Li, L.; Zhou, C.; Chen, L.; Cao, Y.; Gao, Y.; Li, D. Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications. Int. J. Mol. Sci. 2024, 25, 12696. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms252312696](10.3390/ijms252312696) Academic Editor: Elena Bonanno Received: 28 September 2024 Revised: 13 November 2024 Accepted: 16 November 2024 Published: 26 November 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; [13601728046@163.com](13601728046@163.com) (M.F.); [cuihuanhuan@21cn.com](cuihuanhuan@21cn.com) (H.C.); [joshuasen666@163.com](joshuasen666@163.com) (S.L.); [lild0123@163.com](lild0123@163.com) (L.L.); [shiwa1990@163.com](shiwa1990@163.com) (C.Z.); [861025yueyang@163.com](861025yueyang@163.com) (L.C.); [yiqun_fduscc@163.com](yiqun_fduscc@163.com) (Y.C.) 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China * Correspondence: [18111230051@fudan.edu.cn](18111230051@fudan.edu.cn) (Y.G.); [dehengli@fudan.edu.cn](dehengli@fudan.edu.cn) (D.L.)† These authors contributed equally to this work. Abstract: Ubiquitin-Activating Enzyme E1 (UBA1), an E1 enzyme involved in the activation of ubiquitin enzymes, has been involved in the onset and progression of different cancers in humans. Nevertheless, the precise contribution of UBA1 in breast cancer (BC) is still poorly characterized. In this study, a thorough investigation was carried out to elucidate the significance of UBA1 and validate its functionality in BC. Through the analysis of mRNA sequencing data of BC patients, the mRNA expression of UBA1 was observed to be notably enhanced in cancer tissues relative to controls, and high UBA1 expression was linked to worse overall survival (OS), disease-specific survival (DSS), and progress-free survival (PFS) . Moreover, UBA1 exhibited potential as an independent prognostic and diagnostic biomarker for individuals with BC. Additionally, functional enrichment analysis revealed the involvement of UBA1 in inflammation-linked pathways, like the TNF-α signaling pathway, the IL-6 signaling pathway, and various immune-related biological processes. Notably, single-sample gene set enrichment analysis (ssGSEA) aided in the identification of a negative link between UBA1 expression and the levels of infiltrating mast cells, Th1 cells, iDC cells, B cells, DC cells, Tem cells, Cytotoxic cells, T cells, CD8T cells, and pDC cells. Finally, this study demonstrated that silencing UBA1 significantly impeded the growth and development of BC cell lines. These findings highlight UBA1 as a potential prognostic biomarker linked to immune infiltration in BC, thereby depicting its potential as a new therapeutic target for individuals with BC. Keywords: UBA1; breast cancer; prognostic biomarker; immune infiltrates 1. Introduction Breast cancer (BC) is the most prevalent malignancy among females, representing a leading cause of death due to cancer. In recent years, there has been a global increase in the incidence of BC, thereby posing a significant threat to women’s health and well-being and placing a su

FAQs

What is the role of UBA1 considered in this breast cancer study?

UBA1 is an E1 enzyme involved in activating ubiquitin enzymes. The study evaluates how UBA1 contributes to breast cancer onset, progression, and clinical outcomes.

How did researchers assess the clinical significance of UBA1 in breast cancer?

They analyzed mRNA sequencing data to compare UBA1 expression in cancer versus control tissues and correlated high expression with overall survival, disease-specific survival, and progression-free survival.

What immune-related findings connect UBA1 with tumor microenvironment changes?

Enrichment analyses linked UBA1 to inflammation- and immune-associated pathways, and ssGSEA showed UBA1 expression negatively associated with levels of several infiltrating immune cell types.

Does UBA1 have functional effects on breast cancer cells?

Yes. Silencing UBA1 significantly impedes the growth and development of breast cancer cell lines, supporting its potential as a therapeutic target.

Sep 22, 2026

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