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MicroRNA and Non-Coding RNA: From Basic Research to Potential Clinical Application

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 6852

Special Issue Editor

Dr. Erika Cione

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: vitamin A and its provitamin; microRNAs; gene expression; ketogenic diet; lipedema; cognitive and neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Out of the central dogma of molecular biology, messenger RNA (mRNA) is translated into protein. The transcriptome biochemical machinery relies on noncoding RNA (ncRNAs), which, unlike mRNA, is not translated into protein. Such ncRNAs comprise over 80% of the transcriptome by mass and are linked to a growing list of functional roles in human physiology, biology, biochemistry, and disease. RNA modulation has become a promising therapeutic approach for the treatment of several types of disease. The emerging field of noncoding RNA-based biomarkers and/or therapies has now come to the attention of several fields of application, in which it could provide valuable advancements compared to current clinical biochemistry and pharmacological treatment, such as small-molecule drugs or antibodies. Microarray technology and the advent of next-generation sequencing (NGS) have significantly broadened our understanding of ncRNAs in recent decades and introduced new opportunities for clinical applications.

The Special Issue is guest edited by Prof. Dr. Erika Cione, with the assistance of Dr. Diana Marisol Abrego Guandique (University of Magna Graecia-Catanzaro). We would like to gather the recent advances in this field, and we are delighted to invite you to contribute.

Prof. Dr. Erika Cione
Guest Editor

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Keywords

  • miRNA
  • ncRNA
  • biomarkers
  • therapeutics
  • microarray
  • NGS

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Published Papers (5 papers)

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Research

20 pages, 12981 KiB  
Article
MicroRNA Profiling Identifies Age-Associated MicroRNAs and Potential Biomarkers for Early Diagnosis of Autism
by Salam Salloum-Asfar, Samia M. Ltaief, Rowaida Z. Taha, Wared Nour-Eldine, Sara A. Abdulla and Abeer R. Al-Shammari
Int. J. Mol. Sci. 2025, 26(5), 2044; https://doi.org/10.3390/ijms26052044 - 26 Feb 2025
Viewed by 566
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which early diagnosis is critical for effective intervention and improved outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have emerged as promising biomarkers for neurological disorders, including ASD. In our [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which early diagnosis is critical for effective intervention and improved outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have emerged as promising biomarkers for neurological disorders, including ASD. In our previous discovery study, we identified dysregulated expression of several miRNAs in the plasma samples of children with ASD aged 5–12 years. In this study, we aimed to validate these findings in a younger cohort with ASD (aged 2–4 years) and assess their potential use as biomarkers for the early diagnosis of ASD. A total of 108 young children aged 2–4 years were recruited, including 66 children with ASD and 42 age- and sex-matched controls. Using next-generation sequencing and advanced bioinformatics, we validated the differential expression of 17 miRNAs in ASD, which showed consistent dysregulation across both the current and previous cohorts. We also observed significant correlations between several miRNAs and participants’ age, suggesting that age is a key factor influencing dynamic miRNA changes, particularly in the ASD group. Pathway analysis linked these miRNAs to critical regulatory networks involved in neurodevelopment and immune responses. Finally, we found that a combination of four miRNAs (miR-4433b-5p, miR-15a-5p, miR-335-5p, and miR-1180-3p) exhibited high diagnostic accuracy, with an area under the curve (ROC-AUC) of 0.936 (95% CI = 0.892, 0.980; p < 0.001). These findings support the use of this four-miRNA panel as a robust biomarker for early ASD diagnosis and lay the groundwork for future research into miRNA-based diagnostic tools and therapeutic strategies for ASD. Full article
(This article belongs to the Special Issue MicroRNA and Non-Coding RNA: From Basic Research to Potential Clinical Application)
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25 pages, 3766 KiB  
Article
Identification and Functional Analysis of Key microRNAs in the Early Extrauterine Environmental Adaptation of Piglets
by Mingxing Wen, Jing Li, Wanling Qiu, Jinwei Zhang, Keren Long, Lu Lu, Long Jin, Jing Sun, Liangpeng Ge, Xuewei Li, Mingzhou Li and Jideng Ma
Int. J. Mol. Sci. 2025, 26(3), 1316; https://doi.org/10.3390/ijms26031316 - 4 Feb 2025
Viewed by 754
Abstract
Neonatal mammals must rapidly adapt to significant physiological changes during the transition from the intrauterine to extrauterine environments. This adaptation, particularly in the metabolic and respiratory systems, is essential for survival. MicroRNAs (miRNAs) are small noncoding RNAs that regulate various physiological and pathological [...] Read more.
Neonatal mammals must rapidly adapt to significant physiological changes during the transition from the intrauterine to extrauterine environments. This adaptation, particularly in the metabolic and respiratory systems, is essential for survival. MicroRNAs (miRNAs) are small noncoding RNAs that regulate various physiological and pathological processes by binding to the 3′ untranslated regions of mRNAs. This study aimed to identify miRNAs involved in the early extrauterine adaptation of neonatal piglets and explore their functions. We performed small RNA sequencing on six tissues (heart, liver, spleen, lung, multifidus muscle, and duodenum) from piglets 24 h before birth (day 113 of gestation) and 6 h after birth. A total of 971 miRNA precursors and 1511 mature miRNAs were identified. Tissue-specific expression analysis revealed 881 tissue-specific miRNAs and 164 differentially expressed miRNAs (DE miRNAs) across the tissues. Functional enrichment analysis showed that these DE miRNAs are significantly enriched in pathways related to early extrauterine adaptation, such as the NFκB, PI3K/AKT, and Hippo pathways. Specifically, miR-22-3p was significantly upregulated in the liver post-birth and may regulate the PI3K/AKT pathway by targeting AKT3, promoting gluconeogenesis, and maintaining glucose homeostasis. Dual-luciferase reporter assays and HepG2 cell experiments confirmed AKT3 as a target of miR-22-3p, which activates the AKT/FoxO1 pathway, enhancing gluconeogenesis and glucose production. Furthermore, changes in blood glucose and liver glycogen levels in newborn piglets further support the role of miR-22-3p in glucose homeostasis. This study highlights the importance of miRNAs, particularly miR-22-3p, in the early extrauterine adaptation of neonatal piglets, offering new insights into the physiological adaptation of neonatal mammals. Full article
(This article belongs to the Special Issue MicroRNA and Non-Coding RNA: From Basic Research to Potential Clinical Application)
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22 pages, 5135 KiB  
Article
β-Carotene Impacts the Liver MicroRNA Profile in a Sex-Specific Manner in Mouse Offspring of Western Diet-Fed Mothers: Results from Microarray Analysis by Direct Hybridization
by Diana Marisol Abrego-Guandique, Sebastià Galmés, Adrián García-Rodríguez, Roberto Cannataro, Maria Cristina Caroleo, Joan Ribot, Maria Luisa Bonet and Erika Cione
Int. J. Mol. Sci. 2024, 25(23), 12899; https://doi.org/10.3390/ijms252312899 - 30 Nov 2024
Cited by 2 | Viewed by 1125
Abstract
Maternal unbalanced diets cause adverse metabolic programming and affect the offspring’s liver microRNA (miRNA) profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation [...] Read more.
Maternal unbalanced diets cause adverse metabolic programming and affect the offspring’s liver microRNA (miRNA) profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation on the epigenetic remodeling of offspring’s liver microRNAs. Mouse offspring of WD-fed mothers were given a daily placebo (controls) or BC during suckling. Biometric parameters and liver miRNAome by microarray hybridization were analyzed in newly weaned animals. BC sex-dependently impacted the liver triacylglycerol content. The liver miRNAome was also differently affected in male and female offspring, with no overlap in differentially expressed (DE) miRNAs between sexes and more impact in females. Bioinformatic analysis of DE miRNA predicted target genes revealed enrichment in biological processes/pathways related to metabolic processes, regulation of developmental growth and circadian rhythm, liver homeostasis and metabolism, insulin resistance, and neurodegeneration, among others, with differences between sexes. Fifty-five percent of the overlapping target genes in both sexes identified were targeted by DE miRNAs changed in opposite directions in males and females. The results identify sex-dependent responses of the liver miRNA expression profile to BC supplementation during suckling and may sustain further investigations regarding the long-term impact of early postnatal life BC supplementation on top of an unbalanced maternal diet. Full article
(This article belongs to the Special Issue MicroRNA and Non-Coding RNA: From Basic Research to Potential Clinical Application)
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14 pages, 2345 KiB  
Article
The Protective Role of miR-130b-3p Against Palmitate-Induced Lipotoxicity in Cardiomyocytes Through PPARγ Pathway
by Elena Alonso-Villa, Alipio Mangas, Fernando Bonet, Óscar Campuzano, Maribel Quezada-Feijoo, Mónica Ramos, Carlos García-Padilla, Diego Franco and Rocio Toro
Int. J. Mol. Sci. 2024, 25(22), 12161; https://doi.org/10.3390/ijms252212161 - 13 Nov 2024
Cited by 2 | Viewed by 1335
Abstract
Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPARγ) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPARγ causes dilated cardiomyopathy [...] Read more.
Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPARγ) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPARγ causes dilated cardiomyopathy associated with lipotoxicity in mice. miR-130b-3p has been shown to be downregulated in the plasma of idiopathic dilated cardiomyopathy patients, but its role in modulating cardiomyocyte lipotoxicity via PPARγ remains unclear. Our objective was to investigate the protective role of miR-130b-3p against palmitate-induced lipotoxicity in cardiomyocytes through the modulation of the PPARγ signaling pathway. Human cardiomyoblasts were treated with palmitate. Intracellular lipid accumulation and expression of PPARγ and its downstream targets (CD36, FABP3, CAV1, VLDLR) were analyzed. Mitochondrial oxidative stress was assessed via MitoTracker Green and Redox Sensor Red staining and expression of CPT1B and SOD2. Endoplasmic reticulum stress and apoptosis were determined by examining GRP78, ATF6, XBP1s, CHOP, and caspase-3 expression. miR-130b-3p overexpression was achieved using transfection methods, and its effect on these parameters was evaluated. Luciferase assays were used to confirm PPARγ as a direct target of miR-130b-3p. Palmitate treatment led to increased lipid accumulation and upregulation of PPARγ and its downstream targets in human cardiomyoblasts. Palmitate also increased mitochondrial oxidative stress, endoplasmic reticulum stress and apoptosis. miR-130b-3p overexpression reduced PPARγ expression and its downstream signaling, alleviated mitochondrial oxidative stress and decreased endoplasmic reticulum stress and apoptosis in palmitate-stimulated cardiomyoblasts. Luciferase assays confirmed PPARγ as a direct target of miR-130b-3p. Our findings suggest that miR-130b-3p plays a protective role against palmitate-induced lipotoxicity in cardiomyocytes by modulating the PPARγ signaling pathway. Full article
(This article belongs to the Special Issue MicroRNA and Non-Coding RNA: From Basic Research to Potential Clinical Application)
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25 pages, 2287 KiB  
Article
Long Non-Coding RNAs and Alzheimer’s Disease: Towards Personalized Diagnosis
by Maria I. Mosquera-Heredia, Oscar M. Vidal, Luis C. Morales, Carlos Silvera-Redondo, Ernesto Barceló, Ricardo Allegri, Mauricio Arcos-Burgos, Jorge I. Vélez and Pilar Garavito-Galofre
Int. J. Mol. Sci. 2024, 25(14), 7641; https://doi.org/10.3390/ijms25147641 - 11 Jul 2024
Cited by 3 | Viewed by 2309
Abstract
Alzheimer’s disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of [...] Read more.
Alzheimer’s disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up. Full article
(This article belongs to the Special Issue MicroRNA and Non-Coding RNA: From Basic Research to Potential Clinical Application)
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