Background: Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy associated with limited treatment options and poor prognosis. Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B (ARPC1B), a key regulatory protein within the actin cytoskeleton, could play a pivotal role in ccRCC progression. The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.
Methods: ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis (GEPIA) platform, immunohistochemical (IHC) staining on 150 tumor samples along with 30 corresponding normal tissues, and Western blotting (WB) analyses across multiple ccRCC-derived cell lines. Functional assays assessing cell proliferation, colony formation capability, migration, invasion, and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation. Additionally, WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition (EMT) and the Wnt/β-catenin pathway.
Results: The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines, significantly associated with advanced TNM stages, higher Fuhrman grades, and reduced overall survival (OS) (p < 0.001). Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor. Silencing ARPC1B notably impaired ccRCC cellular activities, and tumorigenesis in animal models, whereas augmented ARPC1B expression enhanced these malignant phenotypes. Mechanistically, downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT, indicated by reduced β-catenin, c-Myc, cyclin D1, and ZEB-1 levels, and concurrently increased E-cadherin expression. Additionally, reactivation of the Wnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.
Conclusions: ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway, ultimately enhancing tumor aggressiveness and metastatic potential. Thus, targeting ARPC1B represents a promising therapeutic strategy, warranting further exploration in ccRCC management.
Keywords: Clear cell renal cell carcinoma (ccRCC); Wnt/β-catenin signaling; actin-related protein 2/3 complex subunit 1B (ARPC1B); biomarker; epithelial-to-mesenchymal transition (EMT).
© 2025 The Authors.