The Effect of Metadherin on NF-κB Activation and Downstream Genes in Ovarian Cancer

Abstract

Ovarian cancer (OC) is the most aggressive gynecological cancer. Even with the advances in detection and therapeutics, it still remains clinically challenging and there is a pressing need to identify novel therapeutic strategies. In searching for rational molecular targets, we identified metadherin (MTDH), a multifunctional gene associated with several tumor types but previously unrecognized in OC. In this study, we found the MTDH is overexpressed in OC tissues. Through in vitro assays with overexpression cells, we characterized the role of MTDH. We confirmed MTDH stable overexpression significantly increased the expression of TNF-α, IL-6, IL-8, IL-10, and IL-1β. Interestingly, NF-kappa-B (NF-κB) and MTDH were found in a feed-forward loop motif. Thus, our findings support the notion that the MTDH and NF-κB signaling network contributes to OC traits. MTDH represents a new OC-associated gene that can contribute to insights of OC biology and suggests other treatment strategies.