Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry

Dysregulation of miR-203 by promoter methylation is associated with the development of various cancers. We aimed to explore the underlying link between promoter methylation and miR-203 expression in Kazakh esophageal squamous cell carcinoma (ESCC). MassARRAY® System spectrometry was used to quantita...

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Main Authors: Xiaobin Cui, Xi Chen, Weiwei Wang, Aimin Chang, Lan Yang, Chunxia Liu, Hao Peng, Yutao Wei, Weihua Liang, Shugang Li, Ning Wang, Wei Liu, Jianming Hu, Wenjie Zhang, Lidong Wang, Yunzhao Chen, Feng Li
Format: Article
Language:English
Published: Taylor & Francis Group 2017-08-01
Series:Epigenetics
Subjects:
Online Access:http://dx.doi.org/10.1080/15592294.2017.1349045
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author Xiaobin Cui
Xi Chen
Weiwei Wang
Aimin Chang
Lan Yang
Chunxia Liu
Hao Peng
Yutao Wei
Weihua Liang
Shugang Li
Ning Wang
Wei Liu
Jianming Hu
Wenjie Zhang
Lidong Wang
Yunzhao Chen
Feng Li
author_facet Xiaobin Cui
Xi Chen
Weiwei Wang
Aimin Chang
Lan Yang
Chunxia Liu
Hao Peng
Yutao Wei
Weihua Liang
Shugang Li
Ning Wang
Wei Liu
Jianming Hu
Wenjie Zhang
Lidong Wang
Yunzhao Chen
Feng Li
author_sort Xiaobin Cui
collection DOAJ
description Dysregulation of miR-203 by promoter methylation is associated with the development of various cancers. We aimed to explore the underlying link between promoter methylation and miR-203 expression in Kazakh esophageal squamous cell carcinoma (ESCC). MassARRAY® System spectrometry was used to quantitatively analyze the DNA methylation of 32 CpG sites within miR-203 in 99 Kazakh ESCC and 46 normal esophageal tissues (NETs) with similar population characteristics. We conducted real-time PCR to detect miR-203 expression levels and evaluated their association with methylation. Eleven CpG units within miR-203 promoter were frequently hypermethylated in ESCC compared with NETs (P < 0.05). The hypermethylation of several CpG units positively correlated with age, lower esophagus, constrictive type of ESCC, and moderately differentiated ESCC. Given the involvement of human papillomavirus (HPV) in etiology of ESCC was confirmed from our previous reports, herein we found that CpG units within miR-203 in HPV16-positive ESCC are more heavily methylated. Furthermore, miR-203 expression showed a nearly 4.5-fold decrease in ESCC than NETs (0.206 ± 0.336 vs. 0.908 ± 1.424, P < 0.001) and was significantly associated with lymph node metastasis (P = 0.012). The expression of miR-203 with 11 completely hypermethylated CpG units was approximately 6.5-fold lower than that with at least 1 unmethylated CpG unit (P < 0.001) and especially the CpG_15.16 and CpG_31.32 with higher methylation levels in ESCC tissues exhibited lower expression levels of miR-203, which indicated a reverse association between miR-203 methylation and expression. Hypermethylated miR-203 is a potential biomarker and targeted delivery of miR-203 could therefore serve as a preventive or therapeutic strategy for Kazakh ESCC.
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spelling doaj.art-0ce145ee738b492395402a5a3346d9da2023-09-21T12:43:13ZengTaylor & Francis GroupEpigenetics1559-22941559-23082017-08-0112869870710.1080/15592294.2017.13490451349045Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometryXiaobin Cui0Xi Chen1Weiwei Wang2Aimin Chang3Lan Yang4Chunxia Liu5Hao Peng6Yutao Wei7Weihua Liang8Shugang Li9Ning Wang10Wei Liu11Jianming Hu12Wenjie Zhang13Lidong Wang14Yunzhao Chen15Feng Li16Shihezi University School of MedicineShihezi University School of MedicineZhucheng Maternal and Child Care Service CentrePeople's Hospital of WusuShihezi University School of MedicineShihezi University School of MedicineShihezi University School of MedicineThe First Affiliated Hospital, Shihezi University School of MedicineShihezi University School of MedicineShihezi University School of MedicineShihezi University School of MedicineShihezi University School of MedicineShihezi University School of MedicineShihezi University School of MedicineHenan Key Laboratory for Esophageal Cancer ResearchShihezi University School of MedicineShihezi University School of MedicineDysregulation of miR-203 by promoter methylation is associated with the development of various cancers. We aimed to explore the underlying link between promoter methylation and miR-203 expression in Kazakh esophageal squamous cell carcinoma (ESCC). MassARRAY® System spectrometry was used to quantitatively analyze the DNA methylation of 32 CpG sites within miR-203 in 99 Kazakh ESCC and 46 normal esophageal tissues (NETs) with similar population characteristics. We conducted real-time PCR to detect miR-203 expression levels and evaluated their association with methylation. Eleven CpG units within miR-203 promoter were frequently hypermethylated in ESCC compared with NETs (P < 0.05). The hypermethylation of several CpG units positively correlated with age, lower esophagus, constrictive type of ESCC, and moderately differentiated ESCC. Given the involvement of human papillomavirus (HPV) in etiology of ESCC was confirmed from our previous reports, herein we found that CpG units within miR-203 in HPV16-positive ESCC are more heavily methylated. Furthermore, miR-203 expression showed a nearly 4.5-fold decrease in ESCC than NETs (0.206 ± 0.336 vs. 0.908 ± 1.424, P < 0.001) and was significantly associated with lymph node metastasis (P = 0.012). The expression of miR-203 with 11 completely hypermethylated CpG units was approximately 6.5-fold lower than that with at least 1 unmethylated CpG unit (P < 0.001) and especially the CpG_15.16 and CpG_31.32 with higher methylation levels in ESCC tissues exhibited lower expression levels of miR-203, which indicated a reverse association between miR-203 methylation and expression. Hypermethylated miR-203 is a potential biomarker and targeted delivery of miR-203 could therefore serve as a preventive or therapeutic strategy for Kazakh ESCC.http://dx.doi.org/10.1080/15592294.2017.1349045esophageal squamous cell carcinomakazakhmir-203methylation
spellingShingle Xiaobin Cui
Xi Chen
Weiwei Wang
Aimin Chang
Lan Yang
Chunxia Liu
Hao Peng
Yutao Wei
Weihua Liang
Shugang Li
Ning Wang
Wei Liu
Jianming Hu
Wenjie Zhang
Lidong Wang
Yunzhao Chen
Feng Li
Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry
Epigenetics
esophageal squamous cell carcinoma
kazakh
mir-203
methylation
title Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry
title_full Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry
title_fullStr Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry
title_full_unstemmed Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry
title_short Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell carcinoma by MassARRAY spectrometry
title_sort epigenetic silencing of mir 203 in kazakh patients with esophageal squamous cell carcinoma by massarray spectrometry
topic esophageal squamous cell carcinoma
kazakh
mir-203
methylation
url http://dx.doi.org/10.1080/15592294.2017.1349045
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