Fig. 8: Downregulation of PTPN13 expression is correlated with a positive HBV status, increased c-Myc levels, and elevated glutamine metabolism-related enzyme expression in HCC tissue.

A Correlations between PTPN13 expression and c-Myc, PSPH, and SLC7A1 expression at the mRNA level in 104 HCC tissue samples were assessed and then analyzed by Pearson’s correlation analysis. B Correlations between PTPN13 expression and c-Myc, PSPH, and SLC7A1 expression at the protein level in 80 HCC tissue samples were assessed and then analyzed by Pearson’s correlation analysis. C Representative IHC images of PTPN13, IGF2BP1, c-Myc, PSPH, and SLC7A1 expression. D PTPN13 and IGF2BP1 protein levels were measured in a tissue microarray by IHC analysis and were analyzed according to tumor stage. E Representative IHC images of Ki-67 and c-Myc expression are shown for PTPN13 interference cells with stable IGF2BP1 knockdown by shRNA or control cells in subcutaneous tumors in nude mice. F A schematic model for the tumor suppressive function of PTPN13 in HCC is shown. PTPN13 expression was downregulated by high levels of HBx-induced promoter methylation, and PTPN13 decreased the stability of c-Myc mRNA by competitively binding to IGF2BP1, which inhibited c-Myc-associated oncogenic functions involved in HCC cell proliferation, especially the activation of the serine biosynthesis pathway and glutamine metabolism.