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Updated: Jun 25, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
RGC32 promotes the progression of ccRCC by activating the NF-κB/SHP2/EGFR signaling pathway
Jing Zhang1,2, Yindi Sun2, Kai Tang3
1Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Background:
The role and clinical significance of the response gene to complement 32 (RGC32) in various cancers have been documented, yet its implications in clear cell Renal Cell Carcinoma (ccRCC) remain underexplored.
Methods:
This study investigated RGC32's diagnostic and prognostic relevance in ccRCC using bioinformatics methods with data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The impact of RGC32 on ccRCC progression was assessed through nude mouse tumor assays. Immunohistochemistry evaluated RGC32 levels in ccRCC and adjacent normal tissues, while cell proliferation, migration, and invasion capabilities were analyzed using CCK-8, monoclonal proliferation assays, Transwell, and wound healing assays, respectively. Western blotting measured relevant protein expressions.
Results:
Bioinformatics analysis highlighted RGC32's significant role in ccRCC pathogenesis. Elevated RGC32 expression in ccRCC tissues was linked to disease progression. Functionally, RGC32 was found to enhance the expression of proteins such as p-PI3K, CyclinA1, CyclinD1, p-STAT3, MMP2, MMP3, MMP9, p-SMAD2/3, Snail, Slug, and N-Cadherin via the NF-κB/SHP2/EGFR pathway, while decreasing E-cadherin levels. Moreover, RGC32 facilitated ccRCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
Conclusion:
RGC32 is a pivotal factor in ccRCC development, primarily through the activation of the NF-κB/SHP2/EGFR signaling pathway.
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