Research Paper Advance Articles
RGC32 promotes the progression of ccRCC by activating the NF-κB/SHP2/EGFR signaling pathway
- 1 Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China
- 2 Department of Oncology, Zibo Central Hospital, Zibo, China
- 3 Department of Urology, Zibo Central Hospital, Zibo, China
- 4 College of Traditional Chinese Medicine, Shandong University of Traditional Chinese, Jinan, China
Received: November 16, 2023 Accepted: May 3, 2024 Published: May 27, 2024
https://doi.org/10.18632/aging.205890How to Cite
Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.