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Epigenetic regulation of lncRNA KCNKI5-ASI in gastric cancer

  • 编号:
    00d0b7e8-e859-4a55-bf3d-6d43d6de53cc
  • 作者:
  • 语种:
    英文
  • 期刊:
    CANCER MANAGEMENT AND RESEARCH ISSN:1179-1322 2019 年 11 卷 (8589 - 8602)
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  • 摘要:

    Background: 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 STATS 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.

  • 推荐引用方式
    GB/T 7714:
    Zhang Haiyan,Zhang Zhuo,Wan Dayu, et al. Epigenetic regulation of lncRNA KCNKI5-ASI in gastric cancer [J].CANCER MANAGEMENT AND RESEARCH,2019,11:8589-8602.
  • APA:
    Zhang Haiyan,Zhang Zhuo,Wan Dayu.(2019).Epigenetic regulation of lncRNA KCNKI5-ASI in gastric cancer .CANCER MANAGEMENT AND RESEARCH,11:8589-8602.
  • MLA:
    Zhang Haiyan, et al. "Epigenetic regulation of lncRNA KCNKI5-ASI in gastric cancer" .CANCER MANAGEMENT AND RESEARCH 11(2019):8589-8602.
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