Abstract 4739: miR-627 and histone demethylase JMJD1A as new therapeutic targets in colon cancer

Abstract

Abstract Vitamin D has excellent antitumor activities against various types of cancers, but it cannot be used for cancer therapy due to its side effect of causing hypercalcemia. To understand its mechanism of action in tumor suppression, we investigated the effects of calcitriol (1α,25-dihydroxyvitamin D3, the active form of vitamin D) on microRNA expression in colon cancer cells. We identified miR-627 as the sole microRNA whose expression was stimulated by calcitriol. Furthermore, JMJD1A (jumonji domain containing 1A), the gene encoding a histone demethylase, was identified as the target of miR-627. By downregulating JMJD1A, miR-627 mediated the effects of calcitriol to increase histone H3K9 methylation and to suppress the expression of growth-promoting genes, such as GDF15. Calcitriol also induced miR-627 and downregulated JMJD1A in colon cancer xenografts in nude mice. Overexpression of miR-627 decreased JMJD1A and suppressed colon cancer growth both in vitro and in vivo in the nude mice. In addition, we found that miR-627 expression was decreased in human colon cancer specimens when compared to its levels in the normal colon tissues. Thus, miR-627 plays an important role in the epigenetic action of vitamin D in tumor suppression. miR-627 and JMJD1A may serve as potential targets to exploit the antitumor activity of vitamin D without eliciting its hypercalcemic side effect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4739. doi:1538-7445.AM2012-4739