CRP and HNF1A collaborate to regulate the progression of laryngeal cancer through the Wnt signaling pathway

Abstract

We aim to investigate the regulatory mechanisms of CRP and HNF1A in laryngeal cancer (LC). Bioinformatics identified core genes and associated transcription factors. QRT-PCR evaluated mRNA expressions, while siRNA-transfection induced gene knockdown. Cell proliferation, apoptosis, migration, and invasion were evaluated via CCK-8, flow cytometry, wound-healing, and Transwell. The association between CRP and HNF1A was confirmed through dual luciferase assays, chromatin immunoprecipitation and electrophoretic mobility shift assay. Western blot investigated protein expressions, the association between CRP and the Wnt pathway was evaluated by β-catenin nuclear localization. Nude mouse tumorigenesis experiments validated tumor regulatory effects in vivo. Immunohistochemistry evaluated the in situ expression of proteins within the tumors. FMO2, PTCHD2, AKR1C4, PRSS27, CRP, and ANKRD37 were LC core genes, with HNF1A correlated with CRP. CRP and HNF1A were upregulated in human LC tissues (p < 0.05). CRP/HNF1A knockdown induced decreased proliferation, migration, invasion, and enhanced apoptosis in TU686 cells (p < 0.05), with the correlation between CRP and HNF1A confirmed experimentally. Upon HNF1A-knockdown, CRP, β-catenin, Wnt3a, and Vimentin were downregulated, while E-cadherin was upregulated (p < 0.05). CRP-knockdown inhibited tumor growth and induced altered CRP, Ki67, and HNF1A expression, and consistent expressions for β-catenin, Wnt3a, E-Cadherin, and Vimentin (p < 0.05). CRP and HNF1A promote LC progression through the Wnt signalling pathway and epithelial-mesenchymal transition.