PORCN promotes hepatocellular carcinogenesis via Wnt/β-catenin-dependent manner

BACKGROUND: Porcupine O-acyltransferase (PORCN), a membrane-bound O-acyltransferase, is crucial in Wnt ligand palmitoylation. However, the roles of PORCN in the development of hepatocellular carcinoma (HCC) remain unknown. METHODS: Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) assays, and The Cancer Genome Atlas (TCGA) database were used to study the expression and prognostic values of PORCN in patients with HCC. Following this, Cell Counting Kit-8 (CCK-8), wound-healing tests, Transwell assay, and a xenograft mouse model were employed to examine the effect of PORCN on HCC cells. Finally, the underlying molecular mechanisms involved in cell proliferation and migration caused by PORCN were identified. RESULTS: The protein and messenger RNA (mRNA) levels of PORCN in HCC tissues were higher than those of adjacent normal tissues. The analysis of TCGA database indicated that patients with higher PORCN expression had a lower overall survival (OS) rate. Overexpression of PORCN could promote the proliferation and migration abilities of HCC cells both in vitro and in vivo. Gene set enrichment analysis (GSEA) showed that the effect of PORCN on the biological characteristics of HCC cells mainly centered on the Wnt-β-catenin signaling pathway. Mechanically, immunofluorescence staining and subcellular protein fraction assays showed that PORCN could induce epithelial-mesenchymal transition (EMT) by promoting the translocation of β-catenin from the cytoplasm to nucleus, ultimately promoting the progression of HCC. CONCLUSIONS: The findings of this study suggest that PORCN can promote HCC cell proliferation and migration by stimulating the Wnt-β-catenin signaling pathway. Therefore, PORCN may be a promising therapeutic target for HCC.