Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers
Jingxu Sun,1,* Yongxi Song,1,* Zhenning Wang,1 Guoli Wang,2 Peng Gao,1 Xiaowan Chen,1 Zhaohua Gao,1 Huimian Xu1 1Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Biochemistry and Molecular...
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doaj-6688afdf26b44840bb7022d075230d932020-11-24T21:02:26ZengDove Medical PressOncoTargets and Therapy1178-69302014-05-012014default85386317043Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancersSun JXSong YXWang ZNWang GLGao PChen XWGao ZHXu HM Jingxu Sun,1,* Yongxi Song,1,* Zhenning Wang,1 Guoli Wang,2 Peng Gao,1 Xiaowan Chen,1 Zhaohua Gao,1 Huimian Xu1 1Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Background: MicroRNAs are associated with tumor genesis and progression in various carcinomas. MicroRNA-148a (miR-148a) was reported to have low expression in gastrointestinal cancers, and might be regulated by promoter region DNA methylation. Methods: Bisulfite-modified sequencing was used to determine the promoter region DNA methylation status of human gastrointestinal cancer cell lines. Expression levels of miR-148a in cell lines treated with 5-aza-2′-deoxycytidine were determined by quantitative real-time polymerase chain reaction. Total DNA was extracted from the tissues of 64 patients with gastric cancer and 51 patients with colorectal cancer. Methylation status was determined by methylation-specific polymerase chain reaction. All statistical analyses were performed with SPSS 17.0 software. Results: The promoter regions of genes in human gastrointestinal cancer cell lines were all hypermethylated, except for HT-29, and the expression of miR-148a tended to be higher than in controls after treatment with 5-aza-2′-deoxycytidine. The methylation-specific polymerase chain reaction results showed that 56.25% of gastric cancer tissues and 19.61% of colorectal cancer tissues were hypermethylated. A strong correlation was found between the expression of miR-148a and the methylation status of promoter regions (P<0.001, chi-square test and Pearson’s correlation). Furthermore, promoter region CpG site hypermethylation of miR-148a was correlated with increased tumor size (P=0.01) in gastric cancer after analyzing the correlation between methylation status and clinicopathologic characteristics. Conclusion: The promoter region CpG sites were hypermethylated in gastrointestinal cancers. Promoter region hypermethylation status was associated with the expression of miR-148a and tumor invasiveness in gastric cancer, and may prove to be a new biomarker and method for treating gastric cancer. Keywords: microRNAs, methylation, CpG site, clinicopathologic characteristicshttp://www.dovepress.com/clinical-significance-of-promoter-region-hypermethylation-of-microrna--a17043 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sun JX Song YX Wang ZN Wang GL Gao P Chen XW Gao ZH Xu HM |
spellingShingle |
Sun JX Song YX Wang ZN Wang GL Gao P Chen XW Gao ZH Xu HM Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers OncoTargets and Therapy |
author_facet |
Sun JX Song YX Wang ZN Wang GL Gao P Chen XW Gao ZH Xu HM |
author_sort |
Sun JX |
title |
Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers |
title_short |
Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers |
title_full |
Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers |
title_fullStr |
Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers |
title_full_unstemmed |
Clinical significance of promoter region hypermethylation of microRNA-148a in gastrointestinal cancers |
title_sort |
clinical significance of promoter region hypermethylation of microrna-148a in gastrointestinal cancers |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2014-05-01 |
description |
Jingxu Sun,1,* Yongxi Song,1,* Zhenning Wang,1 Guoli Wang,2 Peng Gao,1 Xiaowan Chen,1 Zhaohua Gao,1 Huimian Xu1 1Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Background: MicroRNAs are associated with tumor genesis and progression in various carcinomas. MicroRNA-148a (miR-148a) was reported to have low expression in gastrointestinal cancers, and might be regulated by promoter region DNA methylation. Methods: Bisulfite-modified sequencing was used to determine the promoter region DNA methylation status of human gastrointestinal cancer cell lines. Expression levels of miR-148a in cell lines treated with 5-aza-2′-deoxycytidine were determined by quantitative real-time polymerase chain reaction. Total DNA was extracted from the tissues of 64 patients with gastric cancer and 51 patients with colorectal cancer. Methylation status was determined by methylation-specific polymerase chain reaction. All statistical analyses were performed with SPSS 17.0 software. Results: The promoter regions of genes in human gastrointestinal cancer cell lines were all hypermethylated, except for HT-29, and the expression of miR-148a tended to be higher than in controls after treatment with 5-aza-2′-deoxycytidine. The methylation-specific polymerase chain reaction results showed that 56.25% of gastric cancer tissues and 19.61% of colorectal cancer tissues were hypermethylated. A strong correlation was found between the expression of miR-148a and the methylation status of promoter regions (P<0.001, chi-square test and Pearson’s correlation). Furthermore, promoter region CpG site hypermethylation of miR-148a was correlated with increased tumor size (P=0.01) in gastric cancer after analyzing the correlation between methylation status and clinicopathologic characteristics. Conclusion: The promoter region CpG sites were hypermethylated in gastrointestinal cancers. Promoter region hypermethylation status was associated with the expression of miR-148a and tumor invasiveness in gastric cancer, and may prove to be a new biomarker and method for treating gastric cancer. Keywords: microRNAs, methylation, CpG site, clinicopathologic characteristics |
url |
http://www.dovepress.com/clinical-significance-of-promoter-region-hypermethylation-of-microrna--a17043 |
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