Oncogenic cooperation of MUC13 and NDRG1 signaling in liver cancer

Background: Liver cancer is one of the leading causes of cancer-related mortality worldwide, highlighting the vital importance of understanding its molecular mechanism for the development of targeted therapies. Mucin 13 (MUC13), a transmembrane glycoprotein, has been associated with the oncogenic processes that cause liver cancer. Our previous studies have shown its significance in promoting cancer cell survival, proliferation, and metastasis. Emerging evidence indicates that NDRG1 (N-Myc downstream regulated gene 1), played a critical role in cell growth, development, stress response, invasion and migration, may also be implicated in the pathogenesis of liver cancer. The current study aims to investigate the influence of the co-expression of MUC13 and NDRG1 on liver cancer progression and determine if their co-expression is correlated with clinical outcomes. Methodology: We employed liver cancer cell lines corresponding to different tumor grades characterized by MUC13 positivity. The expression levels of MUC13 and NDRG1 were evaluated in these cell lines. We performed confocal microscopy for immunofluorescence to examine co-localization of MUC13 and NDRG1. Furthermore, we conducted immunohistochemical analysis of MUC13-positive patient samples to evaluate NDRG1 expression levels. We additionally examined public databases to assess the correlation of NDRG1 and MUC13 expressions with patient survival. Results: We identified a notable association between increased levels of MUC13 expression and elevated NDRG1 expression in MUC13-positive liver cancer cell lines, suggesting a potential interplay that may facilitate cancer progression. Immunofluorescence assays performed on these cell lines provided yields strong evidence of co-localization between MUC13 and NDRG1. Additionally, our studies demonstrated a direct molecular interaction between MUC13 and NDRG1 in liver cancer cells as evidenced by proximity ligation assay (PLA). We further confirmed NDRG1 expression in MUC13-positive and negative patient samples through immunohistochemical staining. To corroborate our findings, we conducted a correlational analysis using public clinical database, which revealed an association between NDRG1 and MUC13 expression levels, suggesting that higher co-expression of these two molecules is linked to poor overall survival (OS) rates. Conclusion: The outcomes of this study indicate a notable co-expression of MUC13 and NDRG1 in liver cancer, potentially highlighting their cooperative involvement in tumor progression.