Polyribonucleotide phosphorylase is overexpressed in hepatocellular cancer, promoting epithelial phenotype maintenance and tumor progression

Fecha de publicación: 01/12/2024 Fecha Ahead of Print: 01/11/2024

Autores de IIS La Fe

• Judith Pérez Rojas

  Autor

Participantes ajenos a IIS La Fe

• Revert-Ros, Francisco
• Ventura, Ignacio
• Prieto-Ruiz, Jesus A.
• Giner-Moreno, Eduardo
• Perez-Cervera, Angela
• Revert, Fernando
• Hernandez-Andreu, Jose Miguel

Grupos

• Hepatología, Cirugia Hepatobiliopancreática y Trasplantes

  

  Leader

  Marina Berenguer Haym

Abstract

Liver cancer, particularly hepatocellular carcinoma (HCC), is a major global health challenge, largely associated with cirrhosis caused by various factors. Prognosis is often guided by molecular and histological classifications. In this study, expression of Polyribonucleotide Phosphorylase (PNPT1) in HCC was investigated to better understand its role in tumor behavior and patient outcomes. The expression of the corresponding protein PNPase was assessed in HCC tissue samples using immunohistochemistry, while RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed via OncoDB. Additionally, PNPT1 silencing in HepG2 cells was followed by gene and protein expression analysis. The results revealed that PNPT1 is overexpressed in HCC tumors, particularly in those expressing E-cadherin. Notably, silencing PNPT1 in HepG2 cells triggered a shift towards a mesenchymal phenotype. In HCC tissues, PNPT1 expression was linked to markers of epithelial phenotype, oxidative stress, and poor prognosis, especially in non-viral HCC cases. These findings suggest that PNPase may play a crucial role in the progression of well-differentiated HCC tumors, serving as a poor prognostic biomarker.

Keywords

• Hepatocellular carcinoma; PNPase; E-cadherin; Collagen I; Mitochondria