MicroRNA - Volume 12, Issue 1, 2023

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease associated with advanced age. It is characterized by cognitive decline and memory loss and accounts for most cases of dementia in older people. AD can be rooted in genetic, epigenetic, or environmental causes. No drugs or other therapeutic agents prevent or delay AD progression. MicroRNAs (miRNAs) are short and uncoded RNAs that can bind to 200 RNAs approximately. By inhibiting or destroying specific messenger RNAs (mRNAs), they control gene expression and broadly affect cellular functions. MiRNAs play important roles in regulating neuronal growth, neuronal differentiation, dendritic spine morphology, and synaptic flexibility in the nervous system. The expression levels of miRNAs are changed in neurological diseases, including AD, suggesting that they play an essential role in the pathogenesis of the disease. Therefore, targeting disrupted miRNAs may be a novel therapeutic approach against AD and offers multiple solutions, including harnessing the beneficial effects of beta-amyloid, reducing tau protein, reducing neuronal cell death, and protecting synapses in AD.

CRISPR/Cas9 is a powerful gene-editing technology. Extensive scientific data exist that the CRISPR/Cas9 system can target small, non-coding, active RNA molecules, including microRNAs (miRNAs). miRNAs have been recognized as key regulators of different cell biological processes, such as the modulation of fibrosis and cardiac hypertrophy, as well as the regulation of cardiomyocytes. Also, it has been demonstrated that miRNAs strongly affect organ evolution, and that the concentration of miRNAs can involve the differentiation, development, and function of different organs. In addition, the current findings clearly indicate that miRNAs can select and control their targets based on their concentrations. CRISPR/Cas9 genome-editing technology is a stronger system for stopping miRNAs than previous methods, including antisense inhibitors. CRISPR/Cas9 tools can be used to eliminate small areas of DNA and determine miRNA in cases where similar groups of miRNAs are in the same strand. Herein, besides other emerging strategies, we critically summarize the recent investigations linking miRNA-targeted therapeutics and CRISPR/Cas9 system to clarify and combine different delivery platforms and cell-fate engineering of miRNAs function and miRNA-based therapeutic intervention in cardiac development, function, and disease. Based on our findings from the literature, it appears that the use of the CRISPR/Cas technology provides new perspectives for understanding the molecular mechanism of cardiovascular disease and can be effective in treating and controlling cardiac development, function, and disease in the future.

Background: Diabetic complications have been studied extensively in recent years. There are very few biomarkers in body fluids that can pinpoint a distinct diabetic complication due to insufficient known specific biomarkers for ischemia. Objective: Identifying microRNA in animal models for each complication could enable early diagnosis of a given complication if verified in humans. MicroRNA (miRNA) profiling has been done in rodent models for a number of diabetic complications, like diabetic glomerular injury, atherosclerosis, cognitive impairment, diabetic wound healing, angiopathy and other complications. Due to multiple differences between rodents and humans, the changes in rabbit skin, considered closer to humans than even pigs, may better simulate human diabetic complications of ischemia. Methods: To study the miRNA profile of rabbits in which diabetes was induced or ischemia was surgically generated, we studied whether diabetes or ischemia-induced specific miRNA could be detected. MicroRNA from the blood of diabetic rabbits and rabbits with local ischemia was collected in PAXgene Blood RNA tubes specifically designed for miRNA isolation and extracted using the PAX gene miRNA extraction kit. The isolated RNA was quality controlled using an RNA analyzer, and further, using RNA seq technology, it was analyzed for distinct miRNAs that were detected in diabetic and non-diabetic rabbits induced with ischemia. Results: A miRNA that was found to be expressed in diabetic rabbits and ischemic rabbits but not in untreated rabbits was miRNA-183. Several miRNAs were differentially expressed across comparison groups, and several upregulated miRNAs were identified being unique to each comparison. In rabbits with a potential diabetic complication of a long-term ischemic model, there was one distinct microRNA, which was highly significantly upregulated in ischemia rabbit (miRNA-133-3p). One miRNA that was highly significantly upregulated in diabetic rabbit but not in ischemic rabbits was miRNA-3074-5p. Only statistically significant results have been considered and analyzed. Conclusion: These findings could lead to a precise and timely diagnosis of a potential single diabetic complication without invasive tissue biopsies and could be a novel tool in the management of diabetic patients developing complications due to the progression of diabetes.

Background and Aim: Nasopharyngeal Carcinoma (NPC) is an upper respiratory tract cancer prevalent in Southeast Asia and related to chronic EBV infection. microRNAs (miRNAs) regulate gene expression implicated in NPC’s carcinogenesis. However, this circulating RNA molecule’s role and clinical utility remain unknown. Therefore, this study examined the circulation of miRNAs and their association with clinical data. Methods: 160 plasma samples of NPC and 80 non-tumor samples were extracted to evaluate and validate the gene expressions. Quantification expression was performed using relative quantification of qPCR analysis level expression methods. The intrinsic cellular roles involving biological signaling in NPC's oncogenesis using Ingenuity Pathways Analysis (IPA) were also used. Results: The results of the quantification significance profiling of NPC samples revealed decreased miR- 29c-3p (fold change 1.16; p<0.05) and increased 195-5p expression (fold change 1.157; p<0.05). Furthermore, the validation of hsa-miR-29c-3p expression on plasma NPC with known tumor vs. non-tumor and significant changes was also performed using a fold change of 4.45 (medians of 31.45 ± 1.868 and 24.96 ± 1.872, respectively; p<0.0005). miR-29c had a 2.14 fold change correlated with T primary status with a median of 31.99±1.319 and 31.35±2.412, respectively (p<0.05). Stage status with fold change 1.99 also had median levels of 31.98±1.105 and 31.21 ± 2.355, respectively (p-value <0.05). Furthermore, the node’s status for the lower expression of miR-29c with fold change 1.17 had median levels of 32.78 ± 2.221 and 31.33 ± 1.689, respectively (p-value of 0.7). Bioinformatics analysis established the roles and functions of miR-29 in NPC progression, cell death and survival, cellular development, cellular function, and cell maintenance by inhibiting COL4A, PI3K, VEGFA, JUN, and CDK6. Conclusion: Overall, we conclude that decreased miR-29c expression is associated with poor clinical status and might inhibit NPC's five target genes.

Background: Obesity is a public health problem worldwide; it has reached pandemic proportions in the last 40 years. Its prevalence in children and adolescents increased from 0.7% to 7.8% between 1975 and 2016. Recently, microRNAs (miRNAs) have been reported as regulatory factors related to molecular functions under different conditions. These can be used as biomarkers of a disease to estimate risks in the early stages. Objective: This study aimed to determine the expression levels of miRNAs associated with childhood obesity and their relationships with biochemical parameters and Health-related Physical Fitness (HRPF). Methods: This was a descriptive cross-sectional study in which a population of 40 children between 6 and 10 years of age of both sexes from Cali, Colombia, was evaluated; the children were classified as 20 normal-weight and 20 obese. Blood biochemistry, HRPF, and miRNA expression levels were determined (hsa-miR-122-5p, hsa-miR-15b-5p, hsa-miR-191-5p, hsa-miR-486-3p, hsa-miR-222-3p. Comparisons were made between the groups, miRNA associations between the studied variables, and linear regression analysis. Results: Twenty normal-weight and 20 obese patients were evaluated. Both groups had an average age of eight years old. The miRNA hsa-miR-122-5p (p < 0.05) was overexpressed in the obese group. According to the linear regression analysis, the amount of adipose tissue may be associated with the production of miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsamiR- 191-5p). Conclusion: Four miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsa-miR- 191-5p) are associated with modifications in biochemical variables of HRPF in this group. Adipose tissue mass could be associated with the production of these miRNAs, thus making them biomarkers of childhood obesity risk.

Background: Neural tube (NT) morphogenesis is reliant on the proper temporospatial expression of numerous genes and synchronized crosstalk between diverse signaling cascades and gene regulatory networks governing key cellular processes. MicroRNAs (miRNAs), a group of small non-coding regulatory RNAs, execute defining roles in directing key canonical pathways during embryogenesis. Objective: In order to comprehend the mechanistic underpinnings of miRNA regulation of NT morphogenesis, we have identified in the current study various miRNAs and their target mRNAs associated with BMP signaling during critical stages of neurulation. Methods: We previously demonstrated the expression of several miRNAs during the critical stages of neurulation (gestational days (GD) 8.5, 9.0, and 9.5) employing high-sensitivity, high-coverage microarrays. In the present study, bioinformatic analyses were used to identify miRNAs differentially expressed (DE) in the embryonic NT that target messenger RNAs (mRNAs) associated with the bone morphogenetic protein (BMP) signaling pathway. RNAs extracted from the developing NT were hybridized to both miRNA and mRNA arrays to evaluate miRNA-mRNA interactions. Results: Bioinformatic analysis identified several DE miRNAs that targeted mRNAs encoding members of (and proteins associated with) the BMP signaling pathway – a signaling cascade central to normal NT development. Conclusion: Identification of the miRNAs and their mRNA targets associated with BMP signaling facilitates a better understanding of the crucial epigenetic mechanisms underlying normal NT development as well as the pathogenesis of NT defects. The current study supports the notion that miRNAs function as key regulators of neural tube morphogenesis via modulation of the BMP signaling cascade. Altered expression of these miRNAs during neurulation may therefore result in NT defects.