MicroRNA (Shariqah, United Arab Emirates)最新文献

MicroRNA abundance as a particular biomarker for precisely identifying cancer metastases has emerged in recent years. The expression levels of miRNA are analyzed to get insights into cancer tissue detection and subtypes. Similar to other cancer types, the miRNA shows high levels of target mRNA dysregulation in association with non-small cell lung carcinoma (NSCLC). Among many promising cancer biomarkers for NSCLC, miR-7-5p has shown significant downregulation in the NSCLC tissues and targets proto-oncogenes like PAK2 and NOVA2. The expression levels of different proto-oncogenes targeting the miR-7-5p in NSCLC showed that the EGFR-mutated NSCLC has an experimental validation. The target validation of the miR-7-5p could be analyzed using SPR (Surface plasmon resonance) based sensors at a single nanoparticle level, such as Au nanocube, due to its high specificity and accountability. Despite being an accountable tool for cancer diagnosis, miRNA-based biomarkers sometimes cause poor diagnostic specificity and reproducibility due to their heterogenicity and immunogenicity in cancer detection. To overcome these shortcomings, the biomarkers need to be validated according to recent clinical studies.

Introduction: Endometriosis, a prevalent gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, poses significant challenges in diagnosis and management due to its unclear pathogenesis and lack of specific biomarkers.

Objective: This study investigates the potential use of microRNAs (miRNAs) as key markers in endometriosis by studying two cohorts of patients (14 patients diagnosed with endometriosis and 15 patients with gynecological benign lesions, different from endometriosis).

Methods: MicroRNA sequencing analysis was tested within data management by a custom pipeline designed by Eurofins Genoma Group.

Results: We identified a specific miRNA expression profile associated with endometriosis to feature specific disease molecular clusters to further elucidate the underlying mechanisms driving endometriosis pathogenesis. Data from the present study suggest a specific miRNA scar for endometriosis compared to other gynecological diseases to develop screening tools in early diagnosis and to ameliorate the management of the disease itself.

Conclusion: This study lays the foundation for the identification of key miRNAs involved in the disease pathogenesis to unveil the molecular signatures in the complex scenario of endometriosis. Further validation and exploration of these findings are needed to develop tools to improve molecular diagnosis and to create a machine-learning prediction algorithm in the future.

Background: Periodontitis destroys the tooth's supporting structures and attachment apparatus. Local or systemic factors can cause it. Traditionally, diagnosis is based on clinical parameters that may not consistently reflect an accurate confirmation. Biochemical and genetic analyses can provide deeper insights. MicroRNAs (miRNAs) regulate the immune and inflammatory response to microbial pathogens. Detecting and evaluating miRNAs can be an important diagnostic parameter. This study aimed to assess the expression of miRNA 146a,200c, and its target gene PTEN to non-surgical periodontal therapy in serum and saliva.

Materials and methods: This interventional comparative study was conducted on 120 patients of both genders, ages between 35 and 55. Non-surgical periodontal therapy (NSPT) scaling and root planing were performed on all subjects, and their saliva and serum samples were collected before and after 8 weeks of NSPT. Quantitative rt-PCR (reverse transcriptase Polymerase Chain Reaction) analysis was conducted on all samples. The statistical analysis was done using SPSS version 22, and comparisons were made using paired t-tests, independent t-tests, and Pearson's correlation coefficient. The statistical significance level was set at a 'P' value of less than 0.05.

Results: It has been observed that there was a significant difference of miRNA in both serum and saliva samples 146a,200c, and the PTEN gene expression, from the beginning to 8 weeks. Significant variation was not observed when comparing the levels between serum and saliva.

Conclusion: miRNA 146A, 200c, and PTEN genes are interrelated with periodontitis. We can consider them as future biomarkers of periodontal diseases.

Introduction: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Introduction: MicroRNAs (miRNAs), a distinct category of non-coding RNAs, exert multifaceted regulatory functions in a variety of organisms, including humans, animals, and plants. The inventory of identified miRNAs stands at approximately 60,000 among all species and 1,926 in Homo sapiens manifests miRNA expression. Their theranostic role has been explored by researchers over the last few decades, positioning them as prominent therapeutic targets as our understanding of RNA targeting advances. However, limited availability of experimentally determined miRNA structures has constrained drug discovery efforts relying on virtual screening or computational methods, including machine learning and artificial intelligence.

Methods: To address this lacuna, miRVim has been developed, providing a repository of human miRNA structures derived from both two-dimensional (MXFold2, CentroidFold, and RNAFold) and three-dimensional (RNAComposer and 3dRNA) structure prediction algorithms, in addition to experimentally available structures from the RCSB PDB repository.

Results: miRVim contains 13,971 predicted secondary structures and 17,045 predicted three-dimensional structures filling the gap of unavailability of miRNA structure data bank. This database aims to facilitate computational data analysis for drug discovery, opening new avenues for advancing technologies such as machine learning-based predictions in the field of RNA biology.

Conclusion: The publicly accessible structures provided by miRVim, available at https://mirna.in/miRVim, offer a valuable resource for the research community, advancing the field of miRNA-related computational analysis and drug discovery.

Background: miRNAs are small non-coding conserved RNA molecules (18-24 nts) that act as crucial gene regulators via post-transcriptional/translational modifications through interacting with the respective mRNAs during various pathophysiological conditions. Recent research has suggested that non-coding RNAs, particularly miRNAs, can be passed from one species to another to regulate gene expression. Since miRNA-mediated gene regulation has not yet been found in Plasmodia, it is hypothesized that erythrocytic miRNAs from Plasmodium falciparum (P. falciparum) could potentially migrate from the cytoplasm to the parasitophorous vacuole developed intracellularly by the parasite to regulate its transcriptome.

Objective: The objective of this study is to investigate the role of trans-kingdom interactions in host-parasite dynamics and their implications for malaria infection.

Methods: Using the trans-kingdom target gene prediction tool, psRNA target server, a total of 15 human erythrocytic miRNAs from 12 distinct families were selected and obtained from miRBase to find potential P. falciparum candidate genes. This study utilized ShinyGO (version 0.80) for gene enrichment analysis with statistical analysis of the selected features. The PPI-network analysis was performed using the Maximal Clique Centrality (MCC) approach, along with the CytoHubba plugin for identifying hub nodes. The PPI network was visualized using Cytoscape version 3.7.

Results: A total of 145 target genes of Pf3D7 were predicted, with the following genes repeatedly targeted: conserved Plasmodium proteins, conserved Plasmodium membrane proteins, PfEMP1, rifin, RAD54, E3 ubiquitin-protein ligase, and transcription factors related genes. Outputs of ShinyGO included enriched GO pathways of 62 uniquely identified Pf3D7 genes with detailed descriptions and visualized networks. For overlapping relationships, a hierarchical clustering tree of enriched gene sets was carried out, along with a genome plot for representing the chromosomal locations of these genes. According to their coding-noncoding distribution chart, most of these genes were found to be members of the coding gene family. Additionally, PPI-network analysis reported the top 10 hub nodes: PFE0400w, MAL13P1.380, MAL7P1.167, PFD0900w, PF11_0243, PFE0440w, PFE1120w, MAL13P1.315, PF08_0126, and MAL8P1.23. Three KEGG pathway diagrams of pfa 05144 for Malaria, pfa 03440 for homologous recombination, and pfa 00750 for vitamin B6 metabolism with identified Pf3D7 genes were drawn and highlighted in red.

Conclusion: The important target genes of Plasmodium falciparum 3D7 were identified by carrying out a trans-kingdom investigation, thus offering preliminary insights into the potential of erythrocytic miRNAs-mediated trans-kingdom regulation.

Background: Publications reveal different outcomes achieved by genetically knocking out a long non-coding microRNA-host-gene (lncMIRHG) versus the administration of pharmacologic antagomirs specifically targeting the guide strand of such intragenic microRNA. This suggests that lncMIRHGs may perform diverse functions unrelated to their role as intragenic miRNA precursors.

Objective: This review synthesizes in silico, in vitro, and in vivo findings from our lab and others to compare the effects of knocking out the long non-coding RNA MIR22HG, which hosts miR- 22, versus administering pharmacological antagomirs targeting miR-22-3p.

Methods: In silico analyses at the gene, pathway, and network levels reveal both distinct and overlapping targets of hsa-miR-22-3p and its host gene, MIR22HG. While pharmacological antagomirs targeting miR-22-3p consistently improve various metabolic parameters in cell culture and animal models across multiple studies, genetic knockout of MIR22HG yields inconsistent results among different research groups.

Results: Additionally, MIR22HG functions as a circulating endogenous RNA (ceRNA) or "sponge" that simultaneously modulates multiple miRNA-mRNA interactions by competing for binding to several miRNAs.

Conclusions: From a therapeutic viewpoint, genetic inactivation of a lncMIRHG and pharmacologic antagonism of the guide strand of its related intragenic miRNA produce different results. This should be expected as lncMIRHGs play dual roles, both as lncRNA and as a source for primary miRNA transcripts.

Introduction: 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.

Methods: 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.

Conclusion: 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.

MicroRNAs have emerged as pivotal post-transcriptional regulators, orchestrating a myriad of cellular processes critical to both normal physiology and pathological conditions, particularly cancer. Among these, miRNAs containing the highly conserved AAAGUGC seed sequence have garnered significant attention due to their multifaceted roles in cancer progression, acting as both oncogenes and tumour suppressors across a wide spectrum of malignancies. This review delves deeply into the evolutionary significance of AAAGUGC seed-containing miRNAs, elucidating their conserved nature and intricate roles in the regulation of cancer-related gene expression networks. We focused on eight specific miRNAs- miR-17-5p, miR-20a-5p, miR-93-5p, miR-106a-5p, miR-106b-5p, miR-519d-3p, miR-526b-3p, and miR-20b-5p -each of which demonstrates context-dependent oncogenic or tumour-suppressive behaviour. Through an indepth exploration of the molecular mechanisms by which these miRNAs modulate critical pathways, we highlighted their capacity to influence essential processes, including cell proliferation, apoptosis, epithelial-to-mesenchymal transition (EMT), metastasis, and drug resistance, reflecting the complexity of their regulatory roles. Furthermore, we dissected the intricate interactions between these miRNAs and their downstream targets, showcasing their diverse contributions to the tumour microenvironment. The implications of miRNA dysregulation in chemotherapy resistance were also explored. In conclusion, AAAGUGC seed-containing miRNAs represent a complex and evolutionarily conserved family with implications in cancer biology. Their ability to modulate multiple oncogenic and tumour-suppressive pathways highlights their potential as therapeutic targets or biomarkers in the context of personalized cancer treatment strategies. This review provides a comprehensive depth of current knowledge while proposing avenues for future research into the therapeutic manipulation of these miRNAs in combating cancer.

Background: Estrogen plays a protective role in vascular health due, in part, to its regulation of endothelial inflammation. However, the mechanism(s) by which estrogen negatively regulates inflammatory signaling pathways is not completely understood. MicroRNAs (miRNAs) are recognized as sensitive and selective regulators of cardiovascular function, inflammation, and disease, yet the effects of 17β-estradiol on the endothelial miRNA profile are largely unknown.

Objective: The aim of this study was to determine the effect of 17β-estradiol on the expression of inflammation-associated miRNAs in endothelial cells in vitro.

Methods: Human Umbilical Vein Endothelial cells (HUVECs) were treated with media in the absence (control) and presence of 17β-estradiol (100 nM) for 24 hr. Thereafter, endothelial cell release of cytokines (IL-6 and IL-8), the intracellular expression of the central protein inflammatory mediator NF-κB, and the levels of inflammatory-associated miRNAs: miR-126, miR-146a, miR-181b, miR-204, and miR-Let-7a, were determined.

Results: 17β-estradiol-treated cells released significantly lower levels of IL-6 (47.6±1.5 pg/mL vs. 59.3±4.9 pg/mL) and IL-8 (36.3±2.3 pg/mL vs. 44.0±2.0 pg/mL). Cellular expression of total NF-κB (26.0±2.8 AU vs. 21.2±3.1 AU) was not different between groups; however, activated NF-κB (Ser536) (12.9±1.7 AU vs. 20.2±2.2 AU) was markedly reduced in 17β-estradiol-treated cells as compared to untreated cells. Furthermore, cellular expressions of miR-126 (1.8±0.3 fold), miR-146a (1.7±0.3 fold), miR-181b (2.1±0.4 fold), miR-204 (1.9±0.4 fold), and miR-Let-7a (1.8±0.3 fold) were markedly increased in response to 17β-estradiol treatment.

Conclusion: These data suggest that the anti-inflammatory effect of 17β-estradiol in endothelial cells may be mediated by miRNAs.