Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Institute of Cardiovascular Regeneration, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, Frankfurt Am Main, 60590, Germany.
Funct Integr Genomics. 2024 Aug 1;24(4):133. doi: 10.1007/s10142-024-01410-2.
Clustered miRNAs consist of two or more miRNAs transcribed together and may coordinately regulate gene expression. Differential expression of clustered miRNAs is found to be controlled by crosstalk of genetic or epigenetic mechanisms. It has been demonstrated that clustered miRNA expression patterns greatly impact cancer cell progression. With the CmirC initiative, we initially developed a comprehensive database to identify copy number variation (CNV) driven clustered miRNAs in cancer. Now, we extended the analysis and identified three miRNAs, mir-96, mir-183, and mir-21, were found to be significantly upregulated in 17 cancer types. Further, CmirC is now upgraded to determine the impact of changes in the DNA methylation status at clustered miRNAs by utilizing The Cancer Genomic Atlas (TCGA) cancer datasets. We examined specific methylation datasets from 9,639 samples, pinpointing 215,435 methylation sites and 27,949 CpG islands with miRNA cluster information. The integrated analysis identified 34 clusters exhibiting differentially methylated CpG sites across 14 cancer types. Furthermore, we determined that CpG islands in the promoter region of 20 miRNA clusters could play a regulatory role. Along with ensuring a straightforward and convenient user experience, CmirC has been updated with improved data browsing and analysis functionalities, as well as enabled hyperlinks to literature and miR-cancer databases. The enhanced version of CmirC is anticipated to play an important role in providing information on the regulation of clustered miRNA expression, and their targeted oncogenes and tumor suppressors. The newly updated version of CmirC is available at https://slsdb.manipal.edu/cmirclust/ .
簇状 miRNA 由两个或多个一起转录的 miRNA 组成，可能协调调节基因表达。发现簇状 miRNA 的差异表达受遗传或表观遗传机制的串扰控制。已经证明，簇状 miRNA 的表达模式对癌细胞的进展有很大的影响。通过 CmirC 计划，我们最初开发了一个综合数据库，以识别癌症中受拷贝数变异 (CNV) 驱动的簇状 miRNA。现在，我们扩展了分析，发现三个 miRNA，mir-96、mir-183 和 mir-21，在 17 种癌症类型中显著上调。此外，CmirC 现在升级为通过利用癌症基因组图谱 (TCGA) 癌症数据集来确定簇状 miRNA 的 DNA 甲基化状态变化的影响。我们检查了来自 9639 个样本的特定甲基化数据集，确定了 215435 个甲基化位点和 27949 个具有 miRNA 簇信息的 CpG 岛。综合分析确定了在 14 种癌症类型中具有差异甲基化 CpG 位点的 34 个簇。此外，我们确定了 20 个 miRNA 簇启动子区域的 CpG 岛可能起调节作用。除了确保用户体验简单方便外，CmirC 还更新了数据浏览和分析功能，并启用了到文献和 miR-cancer 数据库的超链接。增强版的 CmirC 有望在提供有关簇状 miRNA 表达调控及其靶向癌基因和肿瘤抑制基因的信息方面发挥重要作用。更新后的 CmirC 版本可在 https://slsdb.manipal.edu/cmirclust/ 获得。
