Involvement of RUVBL1 in WNT/β-Catenin Signaling in Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of head and neck squamous cell carcinoma (HNSCC), but the causes and molecular mechanisms remain unclear. The wingless-integrated/β-catenin (WNT/β-catenin) signaling pathway plays a vital role in cancer cell proliferation, differentiation, and metastasis, including OSCC. To screen potential β-catenin-associated genes involved in OSCC, the intersection of these genes in the STRING and IMEx databases was assessed using differential expression genes (DEG) from public microarrays, and 22 were further selected to construct a β-catenin-protein interaction network. The top 14 hub genes (node $\text{degree}>10$ ) within the network were selected. Pearson’s correlation analysis showed that β-catenin expression correlated positively with the expression of 11 genes, including AR, BIRC5, CDK6, DKK1, GSK3B, MET, MITF, PARD3, RUVBL1, SLC9A3R1, and SMAD7. A heat map of overall hub gene survival was created, and elevated expression of DKK1 and RUVBL1 was associated with poor survival using the Mantel-Cox test. To identify the function of RUVBL1, colony formation assay, transwell assay, and western blotting revealed that knock-down of RUVBL1 by siRNA decreased H157 and Cal-27 cell proliferation and metastasis by inhibiting β-catenin signaling. These findings suggest that RUVBL1 may serve as a diagnostic and prognostic biomarker for OSCC, as well as a therapeutic target, and may help to uncover additional molecular mechanisms of β-catenin-driven OSCC tumorigenesis.