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Guanine nucleotide-binding protein 2, GNBP2, accelerates the progression of clear cell renal cell carcinoma via regulation of STAT3 signaling transduction pathway

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Abstract

Background

Guanine nucleotide-binding protein 2 (GNBP2) is a GTPase that has critical roles in host immunity and some types of cancer, but its function in clear cell renal cell carcinoma (ccRCC) is not fully understood.

Objective

This work explored the role of GNBP2 in ccRCC progression and the underlying molecular mechanism.

Methods

Two public human cancer databases TNMplot and TISIDB were employed to analyze the expression pattern of GNBP2 during ccRCC progression and the correlation between GNBP2 expression and clinical features of ccRCC patients. GNBP2 functions in ccRCC cells were determined by EdU staining, flow cytometry, scratch wound assay, transwell assay, and xenograft model. Gene expression was evaluated using qPCR, Western blot, immunofluorescence staining, and immunohistochemical staining.

Results

GNBP2 expression was significantly elevated in ccRCC tissues and increased gradually with the increasing tumor grades. Patients with higher GNBP2 expression had shorter overall survival times. Knockdown of GNBP2 suppressed tumor cell proliferation and cell cycle progression and reduced the capability of migration and invasion, while GNBP2 overexpression exhibited protumor effects. GNBP2 silencing by RNA interference significantly inhibited the tumor growth of tumor-bearing nude mice and decreased the proliferation marker Ki67. Mechanistically, GNBP2 downregulation suppressed the STAT3 signaling transduction, as it reduced the phosphorylation of STAT3 and modulated the expression of the target genes, including c-Myc, MMP2, N-cadherin, and E-cadherin.

Conclusion

These findings reveal that GNBP2 promotes ccRCC progression by regulating STAT3 signaling transduction, indicating that GNBP2 might be a promising molecular target for ccRCC therapy.

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Data availability

All data generated or analyzed during this study are included in this article.

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Funding

This study was supported by the fund of Department of Education of Liaoning Province (205180016).

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Authors and Affiliations

  1. Department of Medicine, Soochow University, Jiangsu, China

    Qingfei Cao

  2. Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China

    Qingfei Cao, Jiaji Ma, Weitao Li, Peng Hong, Tong Shen & Ming Tong

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  1. Qingfei Cao
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  2. Jiaji Ma
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  5. Tong Shen
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  6. Ming Tong
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Correspondence to Ming Tong.

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This study does not contain any study with human subjects. Animal experiments were approved by the Ethics Committee of Jinzhou Medical University and were performed following ARRIVE guidelines.

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Cao, Q., Ma, J., Li, W. et al. Guanine nucleotide-binding protein 2, GNBP2, accelerates the progression of clear cell renal cell carcinoma via regulation of STAT3 signaling transduction pathway. Genes Genom 45, 1–11 (2023). https://doi.org/10.1007/s13258-022-01334-w

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