Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression
ABSTRACT Previous studies have shown decreased expression of repulsive guidance molecule member A (RGMa) in colorectal cancer. However, the relationship between the expression levels and promoter DNA methylation status of RGMa and the clinical characteristics of colorectal cancer has not been previously reported. Here, we investigated the expression of RGMa by immunohistochemistry, real-time PCR and western blotting and analyzed the methylation status of the RGMa promoter using Sequenom's MassARRAY platform in colorectal cancer tissues and adjacent normal colorectal tissues. The results showed that RGMa expression was decreased in cancer tissues compared with adjacent normal tissues (p<0.01). Furthermore, a tendency for decreased expression in tumor tissues was observed from Dukes' stage A to stage D (p<0.01). In addition, significantly higher levels of hypermethylation in promoter regions of RGMa were observed in colorectal cancer tissues, compared with those in adjacent normal colorectal tissues (p<0.01). Moreover, the methylation levels of RGMa in tumor tissues were significantly increased in Dukes' stage C and D compared with Dukes' stage A and B (p<0.01). Our results indicate that RGMa expression and promoter methylation status are closely related to colorectal cancer genesis and progression. Determination of the expression level and methylation frequency of RGMa in colorectal cancer tissues may have benefit for early diagnosis and for evaluating patient prognosis.
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- "RGMa has also been found to function in various other processes, such as axon guidance in the developing visual system and in axon tract formation in the embryonic brain in vivo (Monnier et al., 2002; Matsunaga et al., 2004; Tassew et al., 2008), in neural tube closure (Kee et al., 2008), neuronal differentiation (Matsunaga et al., 2006), cell survival (Koeberle et al., 2010), as well as cell migration and adhesion (Lah and Key, 2012). Recently, RGMa has also been implicated in colorectal, prostate, and breast cancer (Li et al., 2011, 2012a,b; Zhao et al., 2012), and in the immune response (Nohra et al., 2010; Mirakaj et al., 2011; Muramatsu et al., 2011). "
ABSTRACT: Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGFβ) superfamily. BMPs mediate a highly conserved signal transduction cascade through the type-I and type-II serine/threonine kinase receptors and intracellular Smad proteins, which regulate multiple developmental and homeostatic processes. Mutations in this pathway can cause various diseases in humans, such as skeletal disorders, cardiovascular diseases, and various cancers. Multiple levels of regulation, including extracellular regulation, help to ensure proper spatiotemporal control of BMP signaling in the right cellular context. The family of repulsive guidance molecules (RGMs) and the type-I transmembrane protein neogenin, a paralog of DCC (Deleted in Colorectal Cancer), have been implicated in modulating the BMP pathway. In this review, we discuss the properties and functions of RGM proteins and neogenin, focusing on their roles in the modulation of BMP signal transduction. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.Molecular Reproduction and Development 07/2013; 80(9). DOI:10.1002/mrd.22199 · 2.68 Impact Factor