Methylation of miRNA-34a Promoter: a Preliminary Study in Vietnamese Breast Cancer Patients
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Abstract
Abstract: Methylation of miRNA-34a (miR-34a) promoter, a target gene of p53 which induces apoptosis, cell cycle arrest or senescence, was reported in many cancer types, including breast cancer, one of the most common malignancies in women. However there has not been any study on miR-34a methylation in Vietnam. Therefore, this research provides the first sight of methylation status of miR-34a promoter in breast cancer in Vietnam. By using methyl-specific PCR (MSP) technique, we found that the frequency of miR-34a promoter methylation in breast tumors and adjacent tissues was 43.3% (13/30) and 13.3% (4/30), respectively. At the transcriptional level, two target genes of miR-34a, AXL and MDM4, were expressed only in the breast tumor where methylation of miR-34a promoter was detected, but not in the adjacent tissue.
Keywords: DNA methylation, microRNA, miR-34a, breast cancer.References
[2] Y. A. Medvedeva, et al., Effects of cytosine methylation on transcription factor binding sites, BMC Genomics (2014) 119.
[3] X. Q. Li, Y. Y. Guo and W. De, DNA methylation and microRNAs in cancer, World J Gastroenterol 9 (2012) 882.
[4] X. Nan, et al., Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex, Nature 6683 (1998) 386.
[5] P. W. Laird, The power and the promise of DNA methylation markers, Nat Rev Cancer 4 (2003) 253.
[6] L. He and G. J. Hannon, MicroRNAs: small RNAs with a big role in gene regulation, Nat Rev Genet 7 (2004) 522.
[7] Y. Saito, T. Nakaoka and H. Saito, microRNA-34a as a Therapeutic Agent against Human Cancer, J Clin Med 11 (2015) 1951.
[8] E. Bandres, et al., Epigenetic regulation of microRNA expression in colorectal cancer, Int J Cancer 11 (2009) 2737.
[9] R. Neves, et al., Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells, BMC Res Notes (2010) 219.
[10] A. Lujambio, et al., A microRNA DNA methylation signature for human cancer metastasis, Proc Natl Acad Sci U S A 36 (2008) 13556.
[11] N. Raver-Shapira, et al., Transcriptional activation of miR-34a contributes to p53-mediated apoptosis, Mol Cell 5 (2007) 731.
[12] L. He, et al., A microRNA component of the p53 tumour suppressor network, Nature 7148 (2007) 1130.
[13] D. Lodygin, et al., Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer, Cell Cycle 16 (2008) 2591.
[14] K. Dheda, et al., Validation of housekeeping genes for normalizing RNA expression in real-time PCR, Biotechniques 1 (2004) 112-4, 116, 118.
[15] E. M. Glare, et al., beta-Actin and GAPDH housekeeping gene expression in asthmatic airways is variable and not suitable for normalising mRNA levels, Thorax 9 (2002) 765.
[16] M. Vogt, et al., Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas, Virchows Arch 3 (2011) 313.
[17] G. Mudduluru, et al., Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer, Oncogene 25 (2011) 2888.
[18] P. Mandke, et al., MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame, PLoS One 8 (2012) e42034.