# Mitochondrial miRNA- miR-181c-5p and mitomiR-106a-5p levels as indicators in cardiovascular disease patients

**Authors:** Ari Nabi, Raya Kh. Yashooa, Tola Abdulsattar Faraj, Karzan Abdulmuhsin Mohammad, Suhad A. Mustafa, Giuseppe Troiano, Mario Dioguari, Abd Al-Bar Al-Farha, Nazzareno Capitanio

PMC · DOI: 10.1007/s11033-026-11617-0 · 2026-03-25

## TL;DR

This study shows that two mitochondrial microRNAs are significantly elevated in cardiovascular disease patients and could serve as non-invasive biomarkers for early detection.

## Contribution

The study identifies hsa-miR-181c-5p and hsa-miR-106a-5p as novel circulating biomarkers for cardiovascular disease in an Iraqi cohort.

## Key findings

- Plasma hsa-miR-181c-5p was three-fold higher in CVD patients compared to controls (p = 0.0001).
- Hsa-miR-106a-5p was four-fold elevated in CVD patients (p = 0.0008) with strong diagnostic accuracy (AUC 0.749).

## Abstract

Mitochondrial dysfunction is a key contributor to the pathophysiology of cardiovascular disease (CVD), one of the leading causes of morbidity and mortality worldwide. Mitochondria-associated microRNAs (mitomiRs) have emerged as critical regulators of mitochondrial homeostasis and cardiac function; however, their clinical utility as circulating biomarkers remains incompletely defined. This study aimed to evaluate the diagnostic potential of circulating hsa-miR-181c-5p and hsa-miR-106a-5p in patients with CVD and to assess their applicability as early, non-invasive biomarkers in an Iraqi cohort.

In this case–control study, plasma samples were obtained from 30 patients with clinically diagnosed cardiovascular disease and 30 age-matched healthy controls. Total RNA was extracted, followed by complementary DNA synthesis. Expression levels of hsa-miR-181c-5p and hsa-miR-106a-5p were quantified using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis.

Plasma levels of hsa-miR-181c-5p were significantly upregulated in CVD patients, exhibiting a three-fold increase compared with controls (p = 0.0001). Likewise, hsa-miR-106a-5p expression was elevated by approximately four-fold in the CVD group (p = 0.0008). ROC analysis demonstrated robust discriminatory power for both miRNAs, with an area under the curve (AUC) of 0.796 for hsa-miR-181c-5p (p = 0.0002) and 0.749 for hsa-miR-106a-5p (p = 0.0010).

Our findings identify circulating hsa-miR-181c-5p and hsa-miR-106a-5p as promising mitomiR-based biomarkers for cardiovascular disease. Their significant upregulation and diagnostic accuracy support their potential role in early, non-invasive detection of CVD and highlight the clinical relevance of mitochondrial miRNA dysregulation in cardiovascular pathology.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995)

## Full-text entities

- **Genes:** LDLR (low density lipoprotein receptor) [NCBI Gene 3949] {aka LDLCQ2}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, MICU1 (mitochondrial calcium uptake 1) [NCBI Gene 10367] {aka CALC, CBARA1, EFHA3, MPXPS, ara CALC}, MFN2 (mitofusin 2) [NCBI Gene 9927] {aka CMT2A, CMT2A2, CMT2A2A, CMT2A2B, CPRP1, HMSN6A}, COX1 (cytochrome c oxidase subunit I) [NCBI Gene 4512] {aka COI, MTCO1}, MIR181C (microRNA 181c) [NCBI Gene 406957] {aka MIRN181C, mir-181c}, MIR17 (microRNA 17) [NCBI Gene 406952] {aka MIR17-5p, MIR91, MIRN17, MIRN91, hsa-mir-17, miR-17}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, RNU6-2 (RNA, U6 small nuclear 2) [NCBI Gene 103625684] {aka RNU6B, RP104, U6-2}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, MIR106A (microRNA 106a) [NCBI Gene 406899] {aka MIRN106A, mir-106, mir-106a}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, SP1 (Sp1 transcription factor) [NCBI Gene 6667]
- **Diseases:** stroke (MESH:D020521), myocardial H/R injury (MESH:C580424), cardiac apoptosis (MESH:D006331), hypoxia (MESH:D000860), cardiac hypertrophy (MESH:D006332), cancer (MESH:D009369), ventricular hypertrophy (MESH:D024741), obesity (MESH:D009765), hypertrophic (MESH:D002312), hypertension (MESH:D006973), heart failure (MESH:D006333), CVD (MESH:D002318), necrotic (MESH:D009336), cardiomyopathy (MESH:D009202), atherosclerosis (MESH:D050197), diabetes (MESH:D003920), Mitochondrial dysfunction (MESH:D028361), dysfunction of mitochondria (MESH:C564971), inflammation (MESH:D007249)
- **Chemicals:** calcium (MESH:D002118), ROS (MESH:D017382), Ca 2 + (-), tricarboxylic acid (MESH:D014233), SYBR  Green (MESH:C098022), ATP (MESH:D000255)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13018044/full.md

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Source: https://tomesphere.com/paper/PMC13018044