Exploration of bladder cancer-associated methylated miRNAs by methylated DNA immunoprecipitation sequencing
Exploration of bladder cancer-associated methylated miRNAs by methylated DNA immunoprecipitation sequencing
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通过甲基化 DNA 免疫沉淀测序探索膀胱癌相关甲基化 miRNA
DOI：
10.2147/ott.s192248
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发表时间：
2019-08
影响因子：
4
通讯作者：
Zhang Shufang
中科院分区：
文献类型：
--
作者：
Gao Xin;Zheng Wenwen;Ye Lili;Wen Xiaohong;Wang Shunlan;Cao Hui;Liu Xi;Huang Denggao;Wang Fei;Zhang Shufang
背景本研究旨在探讨两种表观基因组成分miRNA和DNA甲基化在膀胱癌（BC）中的关系。方法对8例乳腺癌患者癌组织及配对的癌旁正常组织标本进行甲基化DNA免疫沉淀测序和sRNA-Seq分析，以寻找差异甲基化的miRNA基因，并进行差异miRNA分析。筛选受DNA甲基化调控的miRNAs，并利用GO和京都基因与基因组百科全书（KEGG）以及miRNA-mRNA相互作用网络分析其在BC中的功能。结果212个基因的甲基化水平在肿瘤组织和正常组织中存在差异，在转录起始位点和终止位点特异性富集。在这些基因中，154个是高甲基化的，58个是低甲基化的。GO和KEGG通路富集分析表明，差异甲基化的miRNA基因主要富集在肿瘤相关GO术语和信号通路中。MeDIP-Seq和sRNA-Seq数据的成对统计分析显示，在肿瘤和正常组织中分别有154和165个候选甲基化调节基因。值得注意的是，相互作用网络表明，甲基化调控的miRNAs调控了与癌症发展和进展相关的广泛的mRNAs。特别是，通过qRT-PCR验证了最差异表达的miRNA，使得在膀胱癌患者中miR-145- 5 p下调，miR-182- 5 p上调。结论BC中存在大量的miRNA基因发生甲基化修饰。鉴定这些miRNAs表达的变化为BC诊断提供了大量重要信息。
Background The current study aimed to explore the association between two epigenomic components, miRNA and DNA methylation, in bladder cancer (BC). Methods Eight paired samples of tumor tissue and matched adjacent normal tissues from BC patients were subjected to methylated DNA immunoprecipitation sequencing and sRNA-Seq for differentially methylated miRNA genes and differential miRNA analysis. The miRNAs regulated by DNA methylation were screened and their functions involved in BC were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as well as a miRNA–mRNA interaction network. Results The methylation levels of 212 genes were different between tumors and normal tissues with specific enrichment at transcription initiation and termination sites. Among these genes, 154 were hypermethylated and 58 were hypomethylated. GO and KEGG pathway enrichment analysis indicated that differentially methylated miRNA genes were mainly enriched in tumor-associated GO terms and signaling pathways. Pairwise statistical analysis of MeDIP-Seq and sRNA-Seq data showed that there are 154 and 165 candidate methylation-regulated genes in tumors and normal tissues, respectively. Notably, an interaction network indicated that the miRNAs regulated by methylation regulated a broad range of mRNAs associated with cancer development and progression. In particular, the most differentially expressed miRNAs were validated by qRT-PCR, such that miR-145-5p was downregulated and miR-182-5p was upregulated in patients with bladder cancer. Conclusion A large number of miRNA genes were modified by methylation in BC. Identification of changes in the expression of these miRNAs provides a great deal of important information for BC diagnosis.
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影响因子：
--
作者：
Matsushita R;Yoshino H;Enokida H;Goto Y;Miyamoto K;Yonemori M;Inoguchi S;Nakagawa M;Seki N
通讯作者：
Seki N
影响因子：
2.7
作者：
Shivakumar M;Lee Y;Bang L;Garg T;Sohn KA;Kim D
通讯作者：
Kim D
影响因子：
--
作者：
Shindo T;Niinuma T;Nishiyama N;Shinkai N;Kitajima H;Kai M;Maruyama R;Tokino T;Masumori N;Suzuki H
通讯作者：
Suzuki H
影响因子：
4.8
作者：
Ma, Kelong;He, Yinghua;Zhu, Jingde
通讯作者：
Zhu, Jingde
DOI：
10.1016/j.yped.2012.03.010
发表时间：
2013
期刊：
Yearbook of Pediatrics
影响因子：
--
作者：
J. Stockman
通讯作者：
J. Stockman