Pro-Inflammatory Homeobox Gene, ISX, Regulates Tumor growth and Survival in Hepatocellular Carcinoma
Menée sur des échantillons de tissu tumoral et de tissu sain prélevés sur 119 patients atteints d'un carcinome hépatocellulaire et sur 11 patients non atteints, cette étude met en évidence le rôle joué par le gène ISX dans la progression de la maladie
Chronic inflammation drives initiation of hepatocellular carcinoma (HCC) but the underlying mechanisms linking inflammation and tumor formation remain obscure. In this study, we compared the expression of IL-6 (IL6) and CYCLIN D1 (CCND1) with the IL-6 induced homeobox gene ISX (intestine specific homeobox) in 119 paired specimens of HCC and adjacent normal tissues, and also in paired specimens from 11 non-HCC patients. In pathological analysis, ISX exhibited a tumor-specific expression pattern and a high correlation to patient survival time, tumor size, tumor number and progression stage. Enforced expression of ISX accelerated cell proliferation and tumorigenic activity in hepatoma cells through CCND1 induction. In contrast, shRNA-mediated attenuation of ISX in hepatoma cells decreased cell proliferation and malignant transformation in vitro and in vivo. A high positive correlation existed in human hepatoma tumors between ISX and CCND1 expression. Together, our results highlight ISX as an important regulator in hepatoma progression with significant potential as a prognostic and therapeutic target in HCC.