Abstract 2065: DDX20 deficiency enhances NF-κB by impairing NF-κB suppressive-microRNA function and leads to hepatocarcinogenesis

Abstract

Abstract Hepatocellular carcinoma is the third leading cause of cancer mortality worldwide, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we show that DDX20, a DEAD-box protein identified as a tumor suppressor in a recent comprehensive in vivo screening of murine liver cancer, might have a role in human hepatocellular oncogenesis through previously undefined mechanisms. DDX20 expression was frequently decreased in hepatocellular carcinoma cells compared with the hepatocytes in the noncancerous liver tissues from the same patient, as determined by immunohistochemistry using tissue arrays. DDX20-knockdown cells showed enhanced NF-κB activity and higher interleukin-6 expression, a cytokine known to be related to hepatocarcinogenesis. Our microRNA library screening revealed that several microRNAs expressed in hepatocytes, such as miR-140, normally suppress NF-κB activities. The deficiency of DDX20, a component of microRNA-containing ribonucleoprotein complexes, impaired microRNA function and this led to the impairment of the NF-κB-suppressive microRNA function, and consequently, enhanced NF-κB activity. These results indicate that DDX20 deficiency enhances NF-κB activity by impairing NF-κB-suppressive microRNA function and may contribute to hepatocarcinogenesis. “Functional impairment of microRNAs” identified here, induced by aberrant expression or functional abnormalities of the molecules involved in the microRNA pathway, may also be one of the mechanisms of oncogenesis even in other organs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2065.