DNA methylation mediated silencing of microRNA-874 is a promising diagnosis and prognostic marker in breast cancer
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Lei Zhang1,2,*, Da-Li Yan2,*, Fan Yang1,2, Dan-Dan Wang2, Xiu Chen2, Jian-Zhong Wu2, Jin-Hai Tang3,4 and Wen-Jie Xia2
1Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China
2Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, P.R. China
3Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, P.R. China
4Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, P.R. China
*These authors contributed equally to this work
Jin-Hai Tang, email: firstname.lastname@example.org
Wen-Jie Xia, email: email@example.com
Keywords: breast cancer, DNA methylation, miR-874, prognosis, TCGA
Received: August 11, 2016 Accepted: April 17, 2017 Published: May 02, 2017
MicroRNA-874 (miR-874) is downregulated in several human cancers and has been suggested to be a tumor suppressor gene. However, the molecular mechanism of miR-874 downregulation in breast cancer has not been well elucidated. Here we aimed to study the aberrant hyper-methylation of CpG sites with the utility of miR-874 downreregulation in breast cancer and evaluate the clinical function of miR-874 as a prognostic marker. The miR-874 expressions in cells and tissues of two breast cancer lines were measured by real-time PCR. The DNA methylation status of the miR-874 promoter region in 19 pairs of breast cancer and adjacent normal samples was analyzed with Sequenom EpiTYPER MassArray. To evaluate whether miR-874 is a potential prognostic marker in breast cancer, we also explored the clinical long-time follow-up records from The Cancer Genome Atlas (TCGA). We found miR-874 expression was downregulated in 47 pairs of breast cancer tissues. Moreover, univariate and multivariate analysis revealed miR-874 expression may be a prognostic biomarker of overall survival in breast cancer patients. Preconditioning with 5-Aza-CdR in two cell lines elevated miR-874 expressions. The data from Sequenom EpiTYPER MassArray showed that DNA methylation of the promoter region of miR-874 was upregulated and accompanied by decreased miR-874 expression, which was further confirmed by TCGA. After comprehensive considerations, we think miR-874, which might be served as a prognostic biomarker, is mediated by DNA methylation.
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