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ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 11 - 2024 |
doi: 10.3389/fmolb.2024.1481375
This article is part of the Research Topic The Role of Cancer Stem Cells in Tumorigenesis and Development and Related Therapeutic Targets View all articles
NUF2 is Associated with Cancer Stem Cell Characteristics and a Potential Drug Target for Prostate Cancer
Provisionally accepted- 1 Department of Urology, Yantai Yuhuangding Hospital, Yantai, China
- 2 Beijing Ditan Hospital, Capital Medical University, Beijing, Beijing Municipality, China
- 3 Beijing Chaoyang Hospital, Capital Medical University, Beijing, Beijing Municipality, China
- 4 Qingdao University, Qingdao, Shandong Province, China
Background: Cancer stem cells are characterized by self-renewal, clonal tumor initiation capacity, and treatment resistance, which play essential roles in the tumor progression of prostate cancer (PCa). In this study, we aim to explore the features of cancer stemness and characterize the expression of stem cell-related genes for PCa.We downloaded RNA-seq data and related clinical information from The Cancer Genome Atlas (TCGA) database. The mRNA stemness index (mRNAsi) was analyzed for various clinical features, overall survival (OS), and disease-free survival (DFS), and a weighted gene co-expression network analysis (WGCNA) was performed to identify crucial gene modules and key genes, which may play a role in CSCs. The key gene functions were verified using multiple databases, including the TCGA and Gene Expression Omnibus database (GEO). Next, we explored the potential function of the modules and genes obtained using WGCNA using an enrichment analysis. Finally, we performed in vitro experiments for further verification.Results: We found that mRNAsi were higher in PCa tissues than in normal tissues, and the mRNAsi were closely related to the clinical characteristics of PCa. A total of 16 key genes associated with the mRNAsi scores were identified by WGCNA analysis, including NCAPG, NEK2, DLGAP5, CENPA, CENPF, TPX2, GTSE1, KIF4A, NEIL3, CDC25C, UBE2C, CDCA5, MELK, SKA3, NUF2 and BIRC5. These genes were explicitly highly expressed in PCa across TCGA cancers and were validated in 3 independent GEO PCa datasets. The functional annotations of the key genes were linked with the cell proliferation processes. NUF2 may be a potential biomarker for PCa. In vitro experiments showed that knockdown NUF2 reduced the proliferation and migration of PCa cells.The 16 key genes identified in this study significantly correlate with PCa stem cell characteristics and showed prognosis-oriented effects in PCa patients. Further, the NUF2 gene may be used as a drug target for treating PCa.
Keywords: prostate cancer, Cancer cell stemness, WGCNA, mRNAsi, biomarker
Received: 15 Aug 2024; Accepted: 15 Nov 2024.
Copyright: © 2024 Zhang, Liang, Wang, Xia, Yu and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qi Wang, Beijing Ditan Hospital, Capital Medical University, Beijing, Beijing Municipality, China
Liqian Yu, Qingdao University, Qingdao, 266071, Shandong Province, China
Xiaopeng Hu, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100001, Beijing Municipality, China
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