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The deubiquitinase USP25 contributes to stemness and malignant progression of breast cancer by stabilizing C1ql4.

Created on 07 Jul 2026

Authors

Xiao Li, Zhijun Xing, Haotian Fang, Mingzhen Zhao, Qingxia Li, Na Feng, Fan Xu

Published in

Scientific reports. Volume 16. Issue 1. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

Breast cancer (BC) remains one of the most aggressive and life-threatening types of female cancer. Cancer stem cells (CSCs) are closely correlated with the progression and metastasis of cancers. This study aimed to explore the role of ubiquitin-specific peptidase 25 (USP25) in breast cancer metastasis and stemness. Cell counting kit 8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EDU) assay were performed to measure cell viability and proliferation. Xenograft tumor model was established to determine in vivo growth of cancer cells. Flow cytometry was used to measure cell apoptosis. Western blot and qPCR were performed to assess the expression of apoptosis and cancer stemness biomarkers. Cancer cell self-renewal ability was analyzed by the sphere formation assay. Clinical samples were collected to measure the expression of USP25 and C1ql4 (C1q-like 4). Knockdown of USP25 suppressed the in vitro and in vivo growth of breast cancer cells and increased cell apoptosis, inhibited the self-renewal ability, downregulated the expression of cancer stemness biomarkers, and reduced the stability of C1ql4 protein, whereas overexpression of C1ql4 could reverse these effects. The clinical analysis demonstrated that USP25 and C1ql4 were highly expressed in breast cancer tissues and presented a positive correlation. Our data indicated that knockdown of USP25 suppressed the stemness growth of breast cancer cells via reducing the stability of C1ql4 protein. These findings provide USP25/C1ql4 as a potential therapeutic target for breast cancer.

PMID:
42409806
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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