promotes hepatocellular carcinoma progression via a potential PTTG1-β-catenin-c-MYC axis.

() infection is a recognized risk factor for hepatocellular carcinoma (HCC) and is linked to poor overall survival. To explore the underlying mechanisms, RNA sequencing was conducted on HCC tissues from -positive and -negative patients, revealing significant upregulation of pituitary tumor-transforming gene 1 (PTTG1). Gene Set Enrichment Analysis indicated activation of the Wnt/β-catenin pathway. Functional assays demonstrated that PTTG1 overexpression promoted HCC cell proliferation, migration, invasion, and sphere formation, while PTTG1 knockdown suppressed these processes. Excretory-secretory products (ESP) from enhanced PTTG1 expression and partially restored malignant phenotypes in PTTG1-deficient cells. In vivo, PTTG1 overexpression accelerated tumor growth in subcutaneous models, and ESP treatment elevated the protein levels of PTTG1, β-catenin, c-MYC, and CD44. Immunohistochemistry confirmed higher expression of these markers in both human -positive HCC tissues and a rat model of -associated HCC. These findings suggest that infection promotes HCC malignancy and stemness via ESP-induced PTTG1 expression, potentially through Wnt/β-catenin signaling and its downstream targets, including c-MYC and CD44, particularly in the context of the specific carcinogen-driven models used in this study. Further exploration of the PTTG1 pathway may offer insights into potential therapeutic strategies for -associated HCC.