RAD6 Positively Affects Tumorigenesis of Esophageal Squamous Cell Carcinoma by Regulating Histone Ubiquitination of CCNB1

Abstract

AbstractObjective Esophageal carcinoma (ESCA) is deadly cancer worldwide with unknown etiology. This study aimed to investigate the impact and mechanism of RAD6 on the development of Esophageal squamous cell carcinoma (ESCC).Expressions of RAD6A and RAD6B in ESCA were investigated from TCGA dataset and their expressions in tissue sample of ESCA patients and cells were determined. Functional experiments were conducted to explore the impact of RAD6A and RAD6B on malignant characteristics of several kinds of ESCC cells. Animal experiment was established and injected with RAD6A and RAD6B shRNA to evaluate the effect on tumor growth.RAD6A and RAD6B were up-regulated in ESCC cells and tissues. Overexpressed RAD6A and RAD6B similarly increased ESCC cell proliferation, invasion and migration and silencing of RAD6 exerted opposite effects. Knockdown of RAD6A suppressed tumor growth and decreased the level of H2B, as data demonstrated positive correlation between RAD6A and CCNB1 in ESCC tissues.Collectively, this study elucidates that RAD6 is up-regulated in ESCC and promotes the progression of ESCC through up-regulation of CCNB1 to enhance H2B ubiquitination. These evidence provide a novel insight into the pathogenesis of ESCC and might contribute to the development of targeted therapy.