# Uncovering miRNA–Disease Associations Through Graph Based Neural Network Representations

**Authors:** Alessandro Orro

PMC · DOI: 10.3390/biomedicines14020289 · Biomedicines · 2026-01-28

## TL;DR

This paper introduces a graph-based neural network to predict miRNA-disease associations, improving biomarker discovery and disease understanding.

## Contribution

A novel graph-based learning framework that integrates heterogeneous biological data to predict miRNA-disease associations with high accuracy.

## Key findings

- The method achieved an average AUC–ROC of ~98%, outperforming existing computational approaches.
- Predictions were consistent across validation folds and robustness analyses confirmed stability.

## Abstract

Background: MicroRNAs (miRNAs) are an important class of non-coding RNAs that regulate gene expression by binding to target mRNAs and influencing cellular processes such as differentiation, proliferation, and apoptosis. Dysregulation in miRNA expression has been reported to be implicated in many human diseases, including cancer, cardiovascular, and neurodegenerative disorders. Identifying disease-related miRNAs is therefore essential for understanding disease mechanisms and supporting biomarker discovery, but time and cost of experimental validation are the main limitations. Methods: We present a graph-based learning framework that models the complex relationships between miRNAs, diseases, and related biological entities within a heterogeneous network. The model employs a message-passing neural architecture to learn structured embeddings from multiple node and edge types, integrating biological priors from curated resources. This network representation enables the inference of novel miRNA–disease associations, even in sparsely annotated regions of the network. The approach was trained and validated on a dataset benchmark using ten replicated experiments to ensure robustness. Results: The method achieved an average AUC–ROC of ~98%, outperforming previously reported computational approaches on the same dataset. Moreover, predictions were consistent across validation folds and robustness analyses were conducted to evaluate stability and highlight the most important information. Conclusions: Integrating heterogeneous biological information and representing it through graph neural network representation learning offers a powerful and generalizable way to predict relevant associations, including miRNA–disease, and provide a robust computational framework to support biomedical discovery and translational research.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, MIR1193 (microRNA mir-1193) [NCBI Gene 100313107] {aka bta-mir-1193}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, COL4A1 (collagen type IV alpha 1 chain) [NCBI Gene 1282] {aka BSVD, BSVD1, COL4A1s, PADMAL, RATOR}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, MIR208A (microRNA 208a) [NCBI Gene 406990] {aka MIR208, MIRN208, MIRN208A, hsa-mir-208a, miRNA208}, MIRLET7E (microRNA let-7e) [NCBI Gene 406887] {aka LET7E, MIRNLET7E, hsa-let-7e, let-7e}, MIR210 (microRNA 210) [NCBI Gene 406992] {aka MIRN210, mir-210}, MIR99B (microRNA 99b) [NCBI Gene 407056] {aka MIRN99B, mir-99b}, COL2A1 (collagen type II alpha 1 chain) [NCBI Gene 1280] {aka ACG2, ANFH, ANFH1, AOM, COL11A3, EDMMD}, WNT10B (Wnt family member 10B) [NCBI Gene 7480] {aka SHFM6, STHAG8, WNT-12}, ITGA9 (integrin subunit alpha 9) [NCBI Gene 3680] {aka ALPHA-RLC, ITGA4L, RLC}, ASIC1 (acid sensing ion channel subunit 1) [NCBI Gene 538244] {aka ACCN2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, ITGA5 (integrin subunit alpha 5) [NCBI Gene 3678] {aka CD49e, FNRA, VLA-5, VLA5A}
- **Diseases:** osteoarthritis (MESH:D010003), ischemia (MESH:D007511), renal cancer (MESH:D007680), spinal cord injuries (MESH:D013119), renal carcinoma (MESH:D002292), neuronal damage (MESH:D009410), obesity (MESH:D009765), cancer (MESH:D009369), Brain Ischemia (MESH:D002545), knee osteoarthritis (MESH:D020370), Wilms Tumor (MESH:D009396), acidosis (MESH:D000138), osteoporotic vertebral fractures (MESH:D058866), neuroinflammation (MESH:D000090862), inflammatory (MESH:D007249), osteosarcoma (MESH:D012516), cardiovascular, and neurodegenerative disorders (MESH:D019636), MDAs (MESH:D004194), injury to (MESH:D014947), reperfusion injury (MESH:D015427), prostate neoplasms (MESH:D011471), PD (MESH:D010300)
- **Chemicals:** lipid (MESH:D008055)
- **Species:** Bos taurus (bovine, species) [taxon 9913], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938369/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938369/full.md

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Source: https://tomesphere.com/paper/PMC12938369