# isomiRGate: a comprehensive gateway for studying the canonical and modified microRNAomes in Cancer

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2024 · $390,290

## Abstract

PROJECT SUMMARY
According to the statistics provided by the American Cancer Society, in 2023, about 1.9 million new cancer cases
will be diagnosed in the United States, and more than 609K people will die from this disease. Such data firmly
highlights the importance of continued efforts to find new and effective ways to detect and treat cancer, with the
ultimate goal of reducing the number of diagnoses and fatalities. Epitranscriptomics has lately enlarged insights
into the field of cancer biology. RNA modifications occur in coding and non-coding RNAs (ncRNAs), including
microRNAs (miRs). miRs are small single-stranded ncRNAs, which play a crucial role as negative regulators of
gene expression, typically via partial base-pairing complementarity with their target transcripts. Post-
transcriptional modification phenomena associated with miRs, such as imprecise cleavage of the miRNA
sequence and Adenosine-to-Inosine RNA Editing events, can alter the miR canonical sequence and function.
Recently, modified miRs (miR isoforms) have been proposed as potential innovative biomarkers for cancer
diagnosis and surveillance. However, concurrent profiling of modified miRs has yet to be investigated in cancer
properly. Additionally, no online resource offers easy and comprehensive consultation to study miR isoforms in
cancer. Solutions to these gaps would positively impact discovering novel potential cancer biomarkers and
uncovering cancer-related mechanisms associated with a broader miRNAome. Recently, we concurrently
profiled canonical and modified (e.g., shifted or DNA/RNA edited) miRs in >13K adult and pediatric cancer
samples from The Cancer Genome Atlas (TCGA) and The Therapeutically Applicable Research to Generate
Effective Treatments (TARGET) repositories (38 cohorts) (Distefano et al. 2022, Cancer Research). We
accurately identified >8K expressed miR isoforms (>5-fold the canonical miRs). By merging canonical and
modified miRs, we boosted the quality of clustering results by improving the patients’ clinicopathologic
stratification. Additionally, the broader miRNAome profiling uncovered a larger number of significant prognostic
signatures. We also implemented an ad-hoc miR isoform-target prediction method and validated unique targeting
for a shifted miR isoform. Therefore, our proposal intends to outline (1) the function and (2) the post-
transcriptional regulation of the broader miRNAome in a cancer-context manner by in-silico analyses and
experimental validations. Moreover, to make the extensive amount of generated data available to the scientific
community, we propose (3) building isomiRGate, a freely accessible online gateway. isomiRGate platform will
serve as a tool to I) elucidate the role of miR isoforms as potential cancer biomarkers and II) deduce the function
and regulation of the broader miRNAome in cancer. We aim to create a platform, isomiRGate, adaptable to new
analysis methods, holding the potential to lead to the discovery of novel therap...

## Key facts

- **NIH application ID:** 10989238
- **Project number:** 1R21CA287180-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Giovanni Nigita
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,290
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10989238

## Citation

> US National Institutes of Health, RePORTER application 10989238, isomiRGate: a comprehensive gateway for studying the canonical and modified microRNAomes in Cancer (1R21CA287180-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10989238. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*