isomiRTar: a comprehensive portal of pan-cancer 5'-isomiR targeting

Inaccurate cleavage of pri-and pre-miRNA hairpins by Drosha and Dicer results in the generation of miRNA isoforms known as isomiRs. isomiRs with 5'-end variations (5'-isomiRs) create a new dimension in miRNA research since they have different seed regions and distinct targetomes. We developed isomiRTar (https://isomirtar.hse.ru)- a comprehensive portal that allows one to analyze expression profiles and targeting activity of 5'-isomiRs in cancer. Using the Cancer Genome Atlas sequencing data, we compiled the list of 1022 5'-isomiRs expressed in 9282 tumor samples across 31 cancer types. Sequences of these isomiRs were used to predict target genes with miRDB and TargetScan. The putative interactions were then subjected to the co-expression analysis in each cancer type to identify isomiR-target pairs supported by significant negative correlations. Downstream analysis of the data deposited in isomiRTar revealed both cancer-specific and cancer-conserved 5'-isomiR expression landscapes. Pairs of isomiRs differing in one nucleotide shift from 5'-end had poorly overlapping targetomes with the median Jaccard index of 0.06. The analysis of colorectal cancer 5'-isomiR-mediated regulatory networks revealed promising candidate tumor suppressor isomiRs: hsa-miR-203a-3p|+1, hsa-miR-192-5p|+1 and hsa-miR-148a-3p|0. In summary, we believe that isomiRTar will help researchers find novel mechanisms of isomiR-mediated gene silencing in different types of cancer.

Automated summary

Inaccurate cleavage of pri and pre-miRNA hairpins by Drosha and Dicer leads to the generation of miRNA isoforms known as isomiRs. 5'-isomiRs, which have variations at the 5' end, have different seed regions and distinct targetomes, adding a new dimension to miRNA research. The isomiRTar portal was developed to analyze expression profiles and targeting activity of 5'-isomiRs in cancer. Using sequencing data from the Cancer Genome Atlas, a list of 1022 5'-isomiRs expressed in 9282 tumor samples across 31 cancer types was compiled. Co-expression analysis and target prediction were performed to identify isomiR-target pairs with significant negative correlations. The analysis revealed both cancer-specific and cancer-conserved 5'-isomiR expression landscapes, and potential tumor suppressor isomiRs were identified in colorectal cancer.