CmirC update 2024: a multi-omics database for clustered miRNAs

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/ .