Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1
AbstractmiR-218, consisting of miR-218-1 at 4p15.31 and miR-218-2 at 5q35.1, was significantly decreased in esophageal squamous cell carcinoma (ESCC) in our previous study. The aim of this study was to determine whether aberrant methylation is associated with miR-218 repression. Bisulfite sequencing analysis (BSP), methylation specific PCR (MSP), and 5-aza-2′-deoxycytidine treatment assay were applied to determine the methyaltion status of miR-218 in cells and clinical samples. In vitro assays were performed to explore the role of miR-218. Results showed that miR-218-1 was significantly CpG hypermethylated in tumor tissues (81%, 34/42) compared with paired non-tumor tissues (33%, 14/42) (p < 0.05). However, no statistical difference was found in miR-218-2. Accordingly, expression of miR-218 was negatively correlated with miR-218-1 methylation status (p < 0.05). After demethylation treatment by 5-aza-2′-deoxycytidine, there was a 2.53- and 2.40-fold increase of miR-218 expression in EC109 and EC9706, respectively. miR-218 suppressed cell proliferation and arrested cells at G1 phase by targeting 3′ untranslated region (3′UTR) of roundabout guidance receptor 1 (ROBO1). A negative correlation was found between miR-218 and ROBO1 mRNA expression in clinical samples. In conclusion, our results support that aberrant CpG hypermethylation at least partly accounts for miR-218 silencing in ESCC, which impairs its tumor-suppressive function. View Full-Text
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Yang, M.; Liu, R.; Li, X.; Liao, J.; Pu, Y.; Pan, E.; Wang, Y.; Yin, L. Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1. Int. J. Mol. Sci. 2015, 16, 27781-27795.
Yang M, Liu R, Li X, Liao J, Pu Y, Pan E, Wang Y, Yin L. Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1. International Journal of Molecular Sciences. 2015; 16(11):27781-27795.Chicago/Turabian Style
Yang, Miao; Liu, Ran; Li, Xiajun; Liao, Juan; Pu, Yuepu; Pan, Enchun; Wang, Yi; Yin, Lihong. 2015. "Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1." Int. J. Mol. Sci. 16, no. 11: 27781-27795.