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

Cao Qingfei; Ma Jiaji; Li Weitao; Hong Peng; Shen Tong; Tong Ming

doi:10.1007/s13258-022-01334-w

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자료유형: 학술저널

저자정보: Cao Qingfei (The First Affiliated Hospital of Jinzhou Medical University China) Ma Jiaji (The First Affiliated Hospital of Jinzhou Medical University China) Li Weitao (The First Affiliated Hospital of Jinzhou Medical University China) Hong Peng (The First Affiliated Hospital of Jinzhou Medical University China) Shen Tong (The First Affiliated Hospital of Jinzhou Medical University China) Tong Ming (The First Affiliated Hospital of Jinzhou Medical University China)

저널정보: 한국유전학회 Genes & Genomics Genes & Genomics Vol.45 No.1

발행연도: 2023.1

수록면: 1 - 11 (11page)

DOI: 10.1007/s13258-022-01334-w

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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.

#Guanine nucleotide-binding protein 2 · Clear cell renal cell carcinoma · Cell signaling · Signal transducer and transcription activator 3 · Disease progression

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