Deciphering the role of precursor miR-12136 and miR-8485 in the progression of intellectual disability (ID)

Garg, Prekshi; Jamal, Farrukh; Srivastava, Prachi

doi:10.1016/j.ibneur.2022.10.005

Cited by 5 publications

(4 citation statements)

References 58 publications

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“…In contrast to a mouse sepsis model of cecal ligation and puncture, a previous study reported that miR-146b protected against sepsis-induced myocardial injury by suppressing expression of IL-1β and myocardium apoptosis [21]. The largest increase in the mean counts in sepsis occurred with miR-12136, the speci c function of which in sepsis or septic cardiomyopathy is not known, but the miRNA is involved in the process of mRNA translation [22].…”

Section: Discussionmentioning

confidence: 94%

Postmortem analyses of myocardial microRNA expression in sepsis

Lehto,

Saukko,

Säkkinen

et al. 2024

Preprint

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Background Sepsis can lead to myocardial depression, playing a significant role in sepsis pathophysiology, clinical care, and outcome. To gain more insight into the pathophysiology of the myocardial response in sepsis, we investigated the expression of microRNA in myocardial autopsy specimens in critically ill deceased with sepsis and non-septic controls. Materials and methods In this retrospective observational study, we obtained myocardial tissue samples collected during autopsy from adult patients deceased with sepsis (n = 15) for routine histological examination. We obtained control myocardial tissue specimens (n = 15) from medicolegal autopsies of cadavers whose cause of death was injury or who were found dead at home and the cause of death was coronary artery disease with sudden cardiac arrest. RNA was isolated from formalin-fixed paraffin- embedded (FFPE) cardiac samples using the RecoverAll Total Nucleic Acid Isolation Kit for FFPE (Invitrogen). Differentially expressed miRNAs were identified using edgeR v3.32. MicroRNA was considered up- or down-regulated if the false discovery rate was < 0.05 and logarithmic fold change (log2FC) ≥ 1 for up-regulated or log2FC ≤ -1 for down-regulated miRNAs. The mean difference and 95% confidence interval (CI) was calculated for normalized read counts. Predicted miRNA targets were retrieved using Ingenuity Pathway Analysis (IPA) software, and pathway enrichment and classification were performed using PantherDB. Results Differential expression analysis identified a total of 32 miRNAs in the myocardial specimens. Eight miRNAs had a significant change in the mean difference based on the 95% CI, with the largest increase in mean counts in septic samples with hsa-miR-12136 and the highest fold change with hsa-miR-146b-5p. The threshold for down-regulated miRNAs in sepsis compared to controls was obtained with hsa-miR-144-5p and hsa-miR-451a, with the latter having the largest decrease in mean counts and fold decrease. Conclusions Several regulatory miRNAs were up- or down-regulated in the myocardial tissue of patients deceased with sepsis compared to non-septic subjects. The predicted target genes of miRNAs are associated with biological functions related to cardiovascular functions, cell viability, cell adhesion, and regulation of inflammatory and immune response.

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Section: Discussionmentioning

confidence: 94%

Postmortem analyses of myocardial microRNA expression in sepsis

Lehto,

Saukko,

Säkkinen

et al. 2024

Preprint

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“…MiR-33a-5p can inhibit viral infection by targeting eukaryotic translation elongation factor 1A1 ( EEF1A1 ) ( 73 ). Moreover, it has been reported that miR-12136 is highly expressed in the brain tissue and that it plays an crucial role in the development of the nervous system ( 74 ). Therefore, these differentially expressed miRNAs in BM ( Table 3 ) can contribute to nervous system development or alleviate neonatal complications, including coagulation, chronic lung disease, and viral infection.…”

Section: Discussionmentioning

confidence: 99%

Characterization of exosomal microRNAs in preterm infants fed with breast milk and infant formula

Kim,

Song,

et al. 2024

Front. Nutr.

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Breastfeeding not only reduces infection-related morbidity, but also increases growth of preterm infants. Advantages of breast milk (BM) for preterm infants are significant. They continue to be studied. However, because not all preterm infants can receive breastfeeding, bovine-based infant formula (IF) is used as an alternative, which may increase the risk of several preterm complications. Exosomes isolated from biofluids are emerging as biomarkers in research of various diseases. Here, we characterized miRNA contents of exosomes in urine and serum samples of preterm infants who were BM and IF fed and performed transcriptomic analysis of small RNA libraries. We identified significantly up-regulated 6 miRNAs and 10 miRNAs, respectively. Gene Ontology (GO) analysis revealed that target genes of these miRNAs might participate in neuronal development, immunity modulation, detoxification of reactive oxygen species, and transmembrane exchange. Our data suggest that exosome-based systemic screening for preterm infants with breastfeeding might be a screening tool for identifying target molecules involved in therapy for preterm infants in neonatal intensive care unit (NICU) and for future application as nutraceutical formulations or pharmaceuticals.

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“…For example, miR-12136 is significantly downregulated in moderate/very preterm versus term colostrum. miR-12136 abnormal expression can lead to poor brain development causing intellectual disability in the growing fetus [ 55 ]. It was also found to be downregulated in plasma from autism spectrum disorder (ASD) patients [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System

Freiría-Martínez,

Iglesias-Martínez-Almeida,

Rodríguez-Jamardo

et al. 2023

Nutrients

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Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.

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Deciphering the role of precursor miR-12136 and miR-8485 in the progression of intellectual disability (ID)

Cited by 5 publications

References 58 publications

Postmortem analyses of myocardial microRNA expression in sepsis

Postmortem analyses of myocardial microRNA expression in sepsis

Characterization of exosomal microRNAs in preterm infants fed with breast milk and infant formula

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System

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