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

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• MicroRNAs (miRNAs) regulate gene expression through specific seed regions.
• Inaccurate processing of miRNA precursors generates miRNA isoforms known as isomiRs.
• IsomiRs with 5'-end variations (5'-isomiRs) possess distinct seed regions and targetomes, impacting gene regulation.

Purpose of the Study:

• To develop isomiRTar, a comprehensive portal for analyzing 5'-isomiR expression and targeting in cancer.
• To identify and characterize 5'-isomiRs across various cancer types using The Cancer Genome Atlas (TCGA) data.

Main Methods:

• Compiled a list of 1022 5'-isomiRs from 9282 tumor samples across 31 cancer types using TCGA data.
• Predicted target genes for identified 5'-isomiRs using miRDB and TargetScan.
• Performed co-expression analysis to identify robust isomiR-target pairs with significant negative correlations.

Main Results:

• Discovered distinct cancer-specific and conserved 5'-isomiR expression patterns.
• Demonstrated that 5'-isomiRs differing by a single nucleotide shift have largely non-overlapping targetomes (median Jaccard index of 0.06).
• Identified potential tumor suppressor 5'-isomiRs in colorectal cancer, including hsa-miR-203a-3p-+1, hsa-miR-192-5p-+1, and hsa-miR-148a-3p-0.

Conclusions:

• The isomiRTar portal provides a valuable resource for exploring 5'-isomiR expression and targeting in cancer.
• 5'-isomiR variations contribute to the complexity of miRNA-mediated gene silencing.
• This resource facilitates the discovery of novel isomiR-mediated regulatory mechanisms in cancer biology.