Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer
Haiyan Zhang,1 Zhuo Zhang,2 Dayu Wang1 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China; 2Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, ChinaCorrespondence: Dayu WangDepartm...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-09-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/epigenetic-regulation-of-incrna-kcnki5-asi-in-gastric-cancer-peer-reviewed-article-CMAR |
| _version_ | 1818338559273205760 |
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| author | Zhang H Zhang Z Wang D |
| author_facet | Zhang H Zhang Z Wang D |
| author_sort | Zhang H |
| collection | DOAJ |
| description | Haiyan Zhang,1 Zhuo Zhang,2 Dayu Wang1 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China; 2Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, ChinaCorrespondence: Dayu WangDepartment of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, Changchun 130033, ChinaEmail lzyhdhbsjz@126.comBackground: Long noncoding RNAs (lncRNAs) play an important role in gastric cancer. In this study, we aimed to uncover the epigenetic regulatory mechanism of lncRNA KCNK15-AS1 in gastric cancer progression.Patients and methods: Forty patients were included in the study. The expression of KCNK15-AS1 was detected by real-time PCR (RT-PCR), the promoter of KCNK15-AS1 was detected by methylation-specific PCR, and the luciferase assay was performed to detect the relationship between KCNK15-AS1 and miR-21. The relationship of the proteins was explored by an RNA pull-down assay and RNA immunoprecipitation. Chromatin immunoprecipitation was performed to detect the relationship between the promoter and the protein.Results: The expression of KCNK15-AS1 was lower in the tumor tissue compared to the normal tissue. KCNK15-AS1 interacted with miR-21. Both the overexpression of KCNK15-AS1 and the knockdown of the expression of miR-21 inhibited proliferation and promoted apoptosis and decreased the level of MMP-9, bcl-2, and MMP-2 but increased the level of Bax. In addition, the methylation of KCNK15-AS1 was detected in the tumor tissue but was not detected in the normal tissue. Treatment with 5-azacytidine and chidamide decreased the level of DNMT1 and HDAC1 and increased the level of KCNK15-AS1. The RNA pull-down and RNA immunoprecipitation results showed that KCNK15-AS1 interacted with DNMT1 and HDAC1. The ChIP-seq result showed that the promoter of MAPK interacted with DNMT1, and the promoter of AKT and STAT5 interacted with HDAC1.Conclusion: In this study, we identified two regulatory axes, namely KCNK15-AS1-DNMT1-MAPK and KCNK15-AS1-HDAC1-AKT, which were associated with gastric cancer progression. Chidamide and 5-azacytidine might provide new modes for treating gastric cancer.Keywords: lncRNA, KCNK15-AS1, DNMT1, HDAC1, gastric cancer, miR-21 |
| first_indexed | 2024-12-13T15:13:02Z |
| format | Article |
| id | doaj.art-b11d31feab51434baf2fd3ddfc7be543 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-13T15:13:02Z |
| publishDate | 2019-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-b11d31feab51434baf2fd3ddfc7be5432022-12-21T23:40:48ZengDove Medical PressCancer Management and Research1179-13222019-09-01Volume 118589860248730Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancerZhang HZhang ZWang DHaiyan Zhang,1 Zhuo Zhang,2 Dayu Wang1 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China; 2Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, ChinaCorrespondence: Dayu WangDepartment of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, Changchun 130033, ChinaEmail lzyhdhbsjz@126.comBackground: Long noncoding RNAs (lncRNAs) play an important role in gastric cancer. In this study, we aimed to uncover the epigenetic regulatory mechanism of lncRNA KCNK15-AS1 in gastric cancer progression.Patients and methods: Forty patients were included in the study. The expression of KCNK15-AS1 was detected by real-time PCR (RT-PCR), the promoter of KCNK15-AS1 was detected by methylation-specific PCR, and the luciferase assay was performed to detect the relationship between KCNK15-AS1 and miR-21. The relationship of the proteins was explored by an RNA pull-down assay and RNA immunoprecipitation. Chromatin immunoprecipitation was performed to detect the relationship between the promoter and the protein.Results: The expression of KCNK15-AS1 was lower in the tumor tissue compared to the normal tissue. KCNK15-AS1 interacted with miR-21. Both the overexpression of KCNK15-AS1 and the knockdown of the expression of miR-21 inhibited proliferation and promoted apoptosis and decreased the level of MMP-9, bcl-2, and MMP-2 but increased the level of Bax. In addition, the methylation of KCNK15-AS1 was detected in the tumor tissue but was not detected in the normal tissue. Treatment with 5-azacytidine and chidamide decreased the level of DNMT1 and HDAC1 and increased the level of KCNK15-AS1. The RNA pull-down and RNA immunoprecipitation results showed that KCNK15-AS1 interacted with DNMT1 and HDAC1. The ChIP-seq result showed that the promoter of MAPK interacted with DNMT1, and the promoter of AKT and STAT5 interacted with HDAC1.Conclusion: In this study, we identified two regulatory axes, namely KCNK15-AS1-DNMT1-MAPK and KCNK15-AS1-HDAC1-AKT, which were associated with gastric cancer progression. Chidamide and 5-azacytidine might provide new modes for treating gastric cancer.Keywords: lncRNA, KCNK15-AS1, DNMT1, HDAC1, gastric cancer, miR-21https://www.dovepress.com/epigenetic-regulation-of-incrna-kcnki5-asi-in-gastric-cancer-peer-reviewed-article-CMARlncRNA KCNK15-AS1 DNMT1 HDAC1 gastric cancer miR-21 |
| spellingShingle | Zhang H Zhang Z Wang D Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer Cancer Management and Research lncRNA KCNK15-AS1 DNMT1 HDAC1 gastric cancer miR-21 |
| title | Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer |
| title_full | Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer |
| title_fullStr | Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer |
| title_full_unstemmed | Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer |
| title_short | Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer |
| title_sort | epigenetic regulation of incrna kcnki5 asi in gastric cancer |
| topic | lncRNA KCNK15-AS1 DNMT1 HDAC1 gastric cancer miR-21 |
| url | https://www.dovepress.com/epigenetic-regulation-of-incrna-kcnki5-asi-in-gastric-cancer-peer-reviewed-article-CMAR |
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