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Role and mechanism of RPA1 in the development and progression of glioma

  • Authors:
    • Zhiming Zhao
    • Yu Sun
    • Ping Yin
    • Quan Zhang
    • Jianfu Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Weihai Municipal Hospital, Weihai, Shandong 264200, P.R. China, Neurological Intensive Care Unit, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China, Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong 261000, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 163
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    Published online on: June 26, 2025
       https://doi.org/10.3892/etm.2025.12913
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Abstract

Glioma is a highly malignant primary tumor of the central nervous system, characterized by highly invasive behavior and a high recurrence rate. The current treatment options for gliomaoften have unsatisfactory outcomes. Replication protein A1 (RPA1), a component of the RPA heterotrimer, has been identified as a potential oncogene implicated in the development and clinical prognosis of various types of solid tumors, including liver cancer, nasopharyngeal carcinoma and gastrointestinal cancer. However, studies on the associations between RPA1 expression and glioma cell proliferation or patient prognosis are limited, and the underlying mechanisms remain unclear. The aim of the present study was to explore the expression of RPA1 in glioma and its clinical relevance in the clinicopathology and prognosis of glioma. In addition, the biological functions and signal transduction pathways mediated by RPA1 were predicted using bioinformatics analysis to provide basic theoretical support for further mechanistic research and in vivo experiments. The Cancer Genome Atlas (TCGA) data analysis, and reverse transcription‑quantitative PCR, western blot analysis and immunohistochemical (IHC) staining were performed to analyze RPA1 expression in glioma cells or tissues of different grades. The associations between RPA1 expression and various pathological parameters related to tumor cell proliferation and patient prognosis were also investigated. Furthermore, the biological processes and signaling pathways influenced by RPA1‑related target genes were predicted. The results revealed that RPA1 expression varies among different grades of gliomas, with higher World Health Organization (WHO) grades exhibiting higher RPA expression levels. Furthermore, both bioinformatics analysis and IHC staining results revealed that high RPA1 expression was associated with a shorter overall survival (OS). In addition, RPA1 expression exhibited a significant association with WHO glioma grade and key markers of malignancy, namely Ki‑67 expression and p53 mutation status. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that RPA1 may promote the development of glioma through pathways including ‘DNA replication’, ‘Fanconi anemia pathway’, ‘mismatch repair’, ‘homologous recombination’, ‘nucleotide excision repair’ and ‘cell cycle’. In conclusion, RPA1 expression in glioma tissues and cells is positively associated with the degree of glioma malignancy, and high RPA1 expression is associated with a shorter OS in patients with glioma.
View Figures

Figure 1

Bioinformatics analysis of RPA1
expression and survival in glioma. (A) Differential expression of
RPA1 in LGG and GBM glioma tissues compared with normal brain
tissue. (B) Kaplan-Meier curves for the comparison of overall
survival in patients with gliomas according to RPA1 expression
level. Both analyses were performed using data from The Cancer
Genome Atlas via the UALCAN portal. RPA1, replication protein A1;
LGG, low-grade glioma; GBM, glioblastoma; T, tumor; N, normal; HR,
hazard ratio; p(HR), P-value of the HR. *P<0.05.

Figure 2

RPA1 expression is upregulated in
glioma cell lines. (A) Relative mRNA expression of RPA1, (B)
representative western blot images and (C) relative protein
expression of RPA1 in a HA1800 astrocyte cell line and U251, SF295,
A172, and TJ905 glioma cell lines. Quantified data are presented as
the mean ± SD. *P< 0.05, **P< 0.01,
***P< 0.001 and ****P< 0.0001 as
indicated. ns, not significant (P>0.05); RPA1, replication
protein A1.

Figure 3

Representative immunohistochemical
staining images and quantification of RPA1 protein expression in
gliomas of different WHO grades. Representative staining images of
glioma of WHO (A) grade I, (B) grade II, (C) grade III and (D)
grade IV (magnification x400). (E) Quantification of RPA1
expression in the glioma samples of four different grades.
Quantified data are presented as the mean ± SD. *P<
0.05, ***P< 0.001 and ****P< 0.0001 as
indicated. RPA1, replication protein A1; WHO, World Health
Organization.

Figure 4

Immunohistochemical staining images of
RPA1, Ki-67 and p53 in gliomas of different WHO grades.
Representative staining images are shown (magnification, x200).
RPA1, replication protein A1; WHO, World Health Organization.

Figure 5

Kaplan-Meier survival curves for
primary glioma patients with low and high expression levels of
RPA1. The cohort comprised 30 patients with low RPA1 expression and
40 with high RPA1 expression. RPA1, replication protein A1.

Figure 6

Protein-protein interaction network
showing the RPA1 interaction network, generated using the STRING
database. RPA1/3, replication protein A1/3; PRIMPOL, primase and
DNA-directed polymerase; TIPIN, TIMELESS-interacting protein;
FANCM, Fanconi anemia complementation group M protein; APITD1,
apoptosis-inducing, TAF9-like domain-containing protein 1; WRN,
Werner syndrome ATP-dependent helicase; RPA3, replication protein
A1; CLSPN, claspin; MCM2/4/6, minichromosome maintenance complex
component 2/4/6.
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Spandidos Publications style
Zhao Z, Sun Y, Yin P, Zhang Q and Zhang J: Role and mechanism of RPA1 in the development and progression of glioma. Exp Ther Med 30: 163, 2025.
APA
Zhao, Z., Sun, Y., Yin, P., Zhang, Q., & Zhang, J. (2025). Role and mechanism of RPA1 in the development and progression of glioma. Experimental and Therapeutic Medicine, 30, 163. https://doi.org/10.3892/etm.2025.12913
MLA
Zhao, Z., Sun, Y., Yin, P., Zhang, Q., Zhang, J."Role and mechanism of RPA1 in the development and progression of glioma". Experimental and Therapeutic Medicine 30.2 (2025): 163.
Chicago
Zhao, Z., Sun, Y., Yin, P., Zhang, Q., Zhang, J."Role and mechanism of RPA1 in the development and progression of glioma". Experimental and Therapeutic Medicine 30, no. 2 (2025): 163. https://doi.org/10.3892/etm.2025.12913
Copy and paste a formatted citation
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Spandidos Publications style
Zhao Z, Sun Y, Yin P, Zhang Q and Zhang J: Role and mechanism of RPA1 in the development and progression of glioma. Exp Ther Med 30: 163, 2025.
APA
Zhao, Z., Sun, Y., Yin, P., Zhang, Q., & Zhang, J. (2025). Role and mechanism of RPA1 in the development and progression of glioma. Experimental and Therapeutic Medicine, 30, 163. https://doi.org/10.3892/etm.2025.12913
MLA
Zhao, Z., Sun, Y., Yin, P., Zhang, Q., Zhang, J."Role and mechanism of RPA1 in the development and progression of glioma". Experimental and Therapeutic Medicine 30.2 (2025): 163.
Chicago
Zhao, Z., Sun, Y., Yin, P., Zhang, Q., Zhang, J."Role and mechanism of RPA1 in the development and progression of glioma". Experimental and Therapeutic Medicine 30, no. 2 (2025): 163. https://doi.org/10.3892/etm.2025.12913
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