MicroRNA - Current Issue

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a major contributor to global morbidity and mortality. As diagnostic tools for MASLD remain limited, microRNAs (miRs) have garnered attention as promising biomarkers due to their roles in regulating metabolic pathways and reflecting disease states.

This systematic review of clinical studies explores the association between miRNAs and the spectrum of MASLD-related pathologies, including steatosis, fibrosis, and Hepatocellular Carcinoma (HCC). A comprehensive literature search was conducted using PRISMA guidelines, resulting in 44 peer-reviewed studies being included. The review identifies several key miRs, such as miR-122, miR-34a, and miR-193-5p, which are linked to lipid metabolism, insulin resistance, and MASLD severity. Results: Additionally, miR-214 and miR-193-5p are highlighted as potential biomarkers for fibrosis, while miR-21 and miR-34a are implicated in the progression of HCC. These miRs were found in various tissues, including serum, liver, visceral adipose tissue, and ascitic fluid, demonstrating their utility as diagnostic and prognostic tools across the MASLD spectrum.

While miR panels are being developed for clinical assessment, further research is required to confirm their roles in diagnosis and treatment, as well as their integration into routine clinical practice.

Micro ribonucleic acids (miRNAs) are small non-coding RNAs that modulate the expression of various genes. They have an important role in cancer pathogenesis. Differential expression of multiple miRNAs have been used as potential diagnostic and prognostic markers.

Various miRNAs have lately been employed as diagnostic and therapeutic targets in different cancers. This prospective study included untreated pediatric neuroblastoma (NB) patients. In the discovery phase, global miRNA profiling was done using next-generation sequencing (NGS) on biopsy tissue samples of NB patients. In this phase, the top expressing miRNAs were identified and chosen for further validation as circulating miRNA in blood samples of a different set of NB patients by real-time polymerase chain reaction (PCR).

Based on the read counts on the global miRNA profiling in the discovery phase, we found that the miRNA that consistently had high reads across the majority of the NB samples were miRNA 451-a, 19b-3p, 106b-5p, and 21-5p. Of these, we selected miRNA 451-a and 19-b for the validation phase of the study as they had consistent overexpression. In the validation phase, the expression of the circulating miRNA 451-a in the blood was found to be higher. The average value for the relative fold (RF) expression for miRNA 451-a was 1.52.

miRNA 451-a is overexpressed both in the cancer tissue and the blood of NB patients. It can serve as a potential diagnostic marker. Further studies can elucidate its role in the pathogenesis of NB and it could have utility as a therapeutic target.

Critical limb ischemia (CLI) is considered the most severe form of peripheral artery disease (PAD). Nowadays, using stem cells such as mesenchymal stem cells (MSCs) to induce angiogenesis seems like a promising method for CLI therapy. Among the many factors that affect the angiogenesis process, microRNA-126 has an important role. Objective: The goal of this study was to increase the angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) via using microRNA-126.

BMSCs were isolated from male C57BL/6 inbred mice. CLI model was created by femoral artery ligation on C57BL/6 mice. Animals were allocated to control, BMSCs, miR-126, and BMSCsmiR-126 groups, and a defined number of the cells and virus were injected 24 h after surgery. Then, wound-healing assay, functional tests, real-time PCR, histopathological evaluation, and donor cell survival were performed.

Results showed that BMSCs and miR-126 groups had a positive effect on angiogenesis. BMSCs miR-126 group had a significant effect on functional improvements, endothelial cell migration, neovascularization, and muscle restructures. In vivo evaluation showed that miR-126 could increase BMSCs survival and paracrine secretion of angiogenic factors such as VEGF and led to remarkable functional improvements and neovascularization in ischemic tissues.

It can be concluded that the combination uses of BMSCs and miR-126 lead to more effective recovery from ischemic damage compared with using them alone. MiR-126 can be used as a strong modifier to reinforce the angiogenic potential, paracrine secretion, and survival of the BMSCs.

Gaucher disease (GD) occurs due to a mutation in the glucosylceramidase (GBA) gene and is a common lysosomal storage disease. It is well known that there is a strong association between the abnormal expression of miRNAs and various diseases including cancer. These abnormally expressed miRNAs can be used as biomarkers. Interestingly, several studies have reported a linkage between GD with an increased risk of cancer. Therefore, in the current study, we investigated the expression levels of selected miRNAs that are associated with cancers that might have potential use as biomarkers in GD.

Blood samples were collected from 24 healthy volunteers, 6 carriers, and 20 treated patients with type 1 GD. A reverse transcription-quantitative real-time PCR (RT-qPCR) platform was used to analyze the miRNA expression levels.

While carriers had lower relative expressions of miRNA-15a with tumor suppressor effect, and miRNA-150 and miRNA-181b with oncogene effect, treated patients with type 1 GD had lower relative expressions of miRNA-15a and miRNA-125b with tumor suppressor effect and higher relative expression miRNA-21 with oncogene effect (p<0.001, p<0.05, p<0.01, p<0.05, p<0.001, and p<0.05, respectively).

The results suggested that the downregulation of miRNA-15a and miRNA-125b expressions with tumor suppressor effect and the upregulation of miRNA-21 expression with oncogene effect can be indicated to an increased risk for cancers such as multiple myeloma (MM), B-cell lymphoma, leukemia, and hepatocellular carcinoma (HCC) in GD.