Abstract
DNA methyltransferase 3A (Dnmt3a), a de novo methyltransferase, has attracted a great deal of attention for its important role played in tumorigenesis. We have previously demonstrated that melanoma is unable to grow in-vivo in conditions of Dnmt3a depletion in a mouse model. In this study, we cultured the Dnmt3a depletion B16 melanoma (Dnmt3a-D) cell line to conduct a comparative analysis of protein expression con-comitant with Dnmt3a depletion in a melanoma cell line. After two-dimensional separation, by gel electro-phoresis and liquid chromatography, combined with mass spectrometry analysis (1DE-LC-MS/MS), the re-sults demonstrated that 467 proteins were up-regulated and 535 proteins were down-regulated in the Dnmt3a-D cell line compared to the negative control (NC) cell line. The Genome Ontology (GO) and KEGG pathway were used to further analyze the altered proteins. KEGG pathway analysis indicated that the MAPK signaling pathway exhibited a greater alteration in proteins, an interesting finding due to the close relation-ship with tumorigenesis. The results strongly suggested that Dnmt3a potentially controls the process of tu-morigenesis through the regulation of the proteins (JNK1, p38α, ERK1, ERK2, and BRAF) involved in tu-mor-related pathways, such as the MAPK signaling pathway and melanoma pathway.
Highlights
Malignant melanoma, one of the most aggressive of all skin cancers, exhibits a high skin cancer mortality rate [1]
Studies of DNA methyltransferase 3A (Dnmt3a) have focused on its effect on proliferation and apoptosis of hepatocellular carcinoma, colorectal cancer and malignant melanoma [14,15,16] In a previous study we demonstrated that tumor growth inhibition was mediated by Dnmt3a depletion [17]
The expression of Dnmt3b was not affected in the negative control (NC) or Dnmt3a-D cells, which is in concordance with our findings in our previous experiment (see Figure 3 (b) in [17])
Summary
One of the most aggressive of all skin cancers, exhibits a high skin cancer mortality rate [1]. It is well established that malignant melanoma contains at least 50 genes that exhibit differential expression as abnormal methylation changes emerge in the promoter region [3,4,5], and that DNA methylation patterns are established and maintained by the coordinated action of three DNA methyltransferases (Dnmts). It has been demonstrated that Dnmt1 [6,7], Dnmt3a, and Dnmt3b [8] are over-expressed in many malignant tumors [9]. Studies of Dnmt3a have focused on its effect on proliferation and apoptosis of hepatocellular carcinoma, colorectal cancer and malignant melanoma [14,15,16] In a previous study we demonstrated that tumor growth inhibition was mediated by Dnmt3a depletion [17]
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