CDKN3 as a key regulator of G2M phase in triple-negative breast cancer: Insights from multi-transcriptomic analysis

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY IUBMB Life Pub Date : 2025-01-26 DOI:10.1002/iub.2922
Haodi Ma, Yirui Dong, Jiayu Zheng, Shunshun Zhang, Siya Tang, Junxiang Wang, Zhifeng Qu, Xiucheng Li, Li Zeng, Kena Song, Chunyan Liu, Linlin Shi, Qinan Yin, Xuewei Zheng
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引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) remains a significant global health challenge, emphasizing the need for precise identification of patients with specific therapeutic targets and those at high risk of metastasis. This study aimed to identify novel therapeutic targets for personalized treatment of TNBC patients by elucidating their roles in cell cycle regulation. Using weighted gene co-expression network analysis (WGCNA), we identified 83 hub genes by integrating gene expression profiles with clinical pathological grades. A machine learning-based integrative approach further pinpointed 12 prognostic genes, among which CDKN3 exhibited the highest hazard ratio and the most adverse impact on overall survival (OS) in BC patients. Additionally, CDKN3 was identified as an independent prognostic factor for OS prediction. CDKN3 overexpression was confirmed in BC patients and validated at both mRNA and protein levels in BC cells. Knockdown of CDKN3 significantly inhibited the migration and proliferation of BC cells. Cell cycle pathway analysis revealed significant enrichment in G2M-associated pathways in BC patients, with multi-transcriptomic data indicating a close association between enhanced G2M cell cycle activity and CDKN3 upregulation in basal cancer subtypes. Pseudotime analysis further suggested CDKN3 upregulation during the G2M phase at the terminal trajectory of basal cancer subtypes, implying that CDKN3 may drive BC cell progression by promoting G2M cell cycle activity. Mechanistically, CDKN3 knockdown induced G2M cell cycle arrest in TNBC cells by downregulating CCNB2. In conclusion, CDKN3 knockdown effectively inhibits TNBC by arresting the G2M cell cycle, underscoring CDKN3 as a promising therapeutic target in TNBC treatment.

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IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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