A number of JmjC domain-containing histone demethylases have been identified and biochemically characterized in mammalian. JMJD2A is a transcriptional cofactor and enzyme that catalyzes demethylation of histone H3 lysines 9 and 36. Here in this study, we aim to explore the role of JMJD2A in human gastric cancer. Quantitative real-time PCR, Western blot and immunohistochemistry analyses reveal higher expression of JMJD2A in clinical gastric cancer tissues than that in normal gastric mucosa. JMJD2A expression is associated with tumor stage and nodal status, and high level of JMJD2A predicts poor overall and disease-free survival. Univariate and multivariate survival analyses demonstrate that JMJD2A could serve as an independent prognostic factor. Furthermore, we show that inhibition the expression of JMJD2A attenuates the growth and transformation of three lines of gastric cancer cells. Mechanically, JMJD2A knockdown induces apoptosis of gastric cancer cells by up-regulating the expression of proapoptotic proteins and by down-regulating anti-apoptotic protein. Finally, we show that JMJD2A level is correlated with the level of the pro-apoptotic microRNA miR-34a in gastric cancer tissues and JMJD2A represses the expression of miR-34a by decreasing its promoter activity. Those findings demonstrate that JMJD2A regulates gastric cancer growth and serves as an independent prognostic factor, and implicate that JMJD2A may be a promising target for intervention. (C) 2014 Elsevier Inc. All rights reserved.
[1]Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China.
[2]Shanghai Childrens Med Ctr, Dept Gen Surg, Shanghai, Peoples R China.
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