MicroRNA (Shariqah, United Arab Emirates)最新文献

Despite their biological simplicity, microRNA-based organisms, such as RNA viruses, are currently shown to be unexpected threats to mammals, including humans. This situation is exemplified by the COVID-19 pandemic triggered by the spread of SARS-CoV-2. RNA viruses are older than DNA viruses. Indeed, from an evolutionary standpoint, RNA is an older molecule than DNA. The strength of RNA viruses, compared to DNA viruses, resides in their simplicity and instability. The instability of RNA viruses, such as human immunodeficiency virus (HIV) and flu viruses, generates mutants to escape the host's defense mechanisms. A formidable combination of lethality and infectivity was recently achieved by SARS-CoV-2. Complex DNAbased defense systems use Toll-like receptors to intercept viral RNA inside a cell. Activation of Toll-like receptors triggers inflammation and activates lymphocytes and monocytes, causing thromboxane release. In the case of SARS-CoV-2 infection, this process results in cytokine storms and lung thromboembolism. The ongoing pandemic can be envisioned as a struggle between highly evolved complex DNA organisms, i.e., humans, and poorly evolved simple RNA organisms, i.e., SARS-CoV-2 virus. Quite surprisingly, the complex organism has a serious problem defeating the simplistic organism. However, humans are finally developing a new effective weapon in fighting the SARS-CoV-2 virus, paradoxically, RNA-based vaccines. These considerations underscore the relevance of microRNAs as powerful tools in therapeutic and preventive medicine.

Background: The pathogenesis associated with Dengue virus (DENV) infection is marked by the impairment of host immune response. Consequently, the modulation of immune response has emerged as an important therapeutic target for the control of DENV infection. Vitamin D has been shown to regulate the immune response in DENV infection, although the molecular mechanism remains poorly understood. Post-transcriptional regulation of mRNA by miRNAs offers an opportunity to gain insight into the immunomodulation mediated by vitamin D.

Objective: Previously, it has been observed that a high dose of vitamin D (4000 IU) decreased DENV-2 infection and inflammatory response in monocyte-derived macrophages (MDMs). Here, we examine whether high or low doses of vitamin D supplements exert differential effect on miRNA expression in DENV-infected macrophages.

Methods: We analyzed miRNA expression profiles in MDMs isolated from healthy individuals who were given either 1000 or 4000 IU/day of vitamin D for 10 days. MDMs before or after vitamin D supplementation were challenged with DENV-2, and miRNAs profiles were analyzed by qPCR arrays.

Results: DENV-2 infected MDMs supplemented with 4000 IU, showed up-regulation of miR-374a-5p, miR-363-3p, miR-101-3p, miR-9-5p, miR-34a-5p, miR-200a-3p, and the family of miRNAs miR-21-5p, and miR-590-p. The miRNA profile and predicted target mRNAs suggested regulatory pathways in MDMs obtained from healthy donors who received higher doses of vitamin D. These DENV-2 infected MDMs expressed a unique set of miRNAs that target immune and cellular stress response genes.

Conclusion: The results suggest vitamin D dose-dependent differential expression of miRNAs target key signaling pathways of the pathogenesis of dengue disease.

MicroRNAs (miRNAs), small non-coding RNAs, participate in the transcriptional and post-transcriptional regulation of eukaryotic genes, and are potential biomarkers for diseases. Mature miRNAs can be located in both the nucleus and cytoplasm, where they perform their regulatory function. The discovery of new miRNAs and the identification of their targets and functions are fundamental to understanding the biological processes regulated by them, as well as the role they play in diseases. This present study researched miRNAs function at nuclear level and as circulating molecules.

MicroRNAs (miRNAs) are small non-coding RNAs (19~25 nucleotides) that regulate gene expression at a post-transcriptional level through repression of mRNA translation or mRNA decay. MiR-147, which was initially discovered in mouse spleen and macrophages, has been shown to correlate with coronary atherogenesis and inflammatory bowel disease and modulate macrophage functions and inflammation through TLR-4. Altered miR-147 level has been shown in various human diseases, including infectious disease, cancer, cardiovascular disease, neurodegenerative disorder, etc. This review will focus on the current understanding regarding the role of miR-147 in inflammation and diseases.

Background: Several studies have reported a possible association of miR-146a rs2910164 polymorphism with Breast Cancer (BC) development. However, the correlation between this polymorphism and susceptibility to BC is under debate. The current meta-analysis was designed and performed to more conclusively evaluate the miR-146a rs2910164 polymorphism and its potential link to BC.

Methods: Our team has selected eligible studies (published up to October 2, 2020) from several electronic databases, including Web of Science, PubMed, Scopus and Google Scholar. A total number of 9,545 BC cases and 10,030 controls extracted from 26 eligible articles were included in this study. We utilized pooled Odds Ratios (ORs) as well as 95% confidence intervals (95% CIs) under five genetic models for quantitative estimation of any possible association between miR-146a rs2910164 polymorphism and BC.

Results: Based on this meta-analysis, our findings suggest that there is no significant association between miR-146a rs2910164 polymorphism and BC risk. However, stratified analysis revealed that the rs2910164 polymorphism significantly increased the risk of BC in hospital-based studies using the homozygous genetic model (OR=1.37, 95%CI=1.01-1.86, p=0.043, CC vs. GG). Neither Asian nor Caucasian populations showed any significant association between rs2910164 polymorphism and BC susceptibility.

Conclusion: In summary, our findings suggest that BC development is not associated with miR-146a rs2910164 polymorphism. However, larger ingenious future investigations might be needed for a more precise estimation of any association between miR-146a rs2910164 polymorphism and BC.

Background: Ovarian cancer is the most deadly cancer that requires novel diagnostics and therapeutics. MicroRNAs are viewed as essential gene regulatory elements involved in different pathobiological mechanisms of many cancers, including ovarian cancer.

Objective: This study examined the relationship between microRNA (miRNA) expression and response to platinum-based chemotherapy.

Methods: Genome-wide miRNA expression analysis was conducted using Epithelial Ovarian Cancer (EOC) tissues from 25 patients with 17 malignant tumors and eight benign ovarian tumors. Candidate miRNAs that respond to platinum-based chemotherapy were selected for validation by quantitative RT-PCR.

Results: Among 2,578 mature human miRNAs, high expression of miR-483-5p correlated with poor responses to platinum-based chemotherapy in EOC patients. Furthermore, high levels of miR-483-5p in the resistant group suppressed expression of the apoptotic regulator TAOK-1.

Conclusion: A possible marker for the prediction of chemotherapy response and resistance in patients may be miR-483-5p. Choosing the right treatment for each patient with EOC can avoid the risk of developing chemotherapy resistance.

Background: miR-21, miR-214 and miR-let-7a are three validated and well-known miRNAs. miR-21 is described as an "oncomir" while miR-214 and miR-let-7a are described mainly as tumor suppressors. The role of these miRNAs remains unclear in cervical cancer, an important malignancy among women worldwide and responsible for many deaths every year.

Objective: The objective of this study is to describe the expression profile of miR-21, miR-214 and miR-let-7a in plasma and in cervical scraping from a control group and patients with different grades of cervical lesions and invasive cervical cancer and correlate with HPV infection groups.

Methods: Plasma and cervical scraping were submitted to DNA and RNA extraction. HPV detection and typing were performed by conventional PCR followed by PAGE to amplicons interpretation. The miRNA relative expression in plasma and cervical scraping samples was performed by real time PCR using specific TaqMan probes.

Results: miR-21 (p=0.0277) and miR-214 (p=0.0151) were up-regulated in cervical scraping samples of invasive cervical cancer (ICC) group. However, miR-214 was also up-regulated in the LSIL group (p=0.0062). Both miRNAs were not related to HPV infection. However, miR-let-7a was higher in HPV positive plasma samples (p=0.0433) than in HPV negative plasma samples and the correlation analysis confirmed the association between the levels of this miRNA with the presence of HPV (p=0.0407; r=0.3029), but not with lesion grade (p>0.05).

Conclusion: Our results suggest that miR-21 is related to cervical cancer progression and miR-214 appears to have an ambiguous role in cervical lesions. miR-let-7a may be upregulated at a systemic level in patients with HPV infection.

Background: Bronchial Asthma (BA) and Chronic Obstructive Pulmonary Disease (COPD) are chronic airway inflammation diseases. In recent years, patients with signs of both BA and COPD have been assigned to a separate group as Asthma-COPD Overlap Syndrome (ACOS). Free-circulating plasma microRNAs are considered as potential biomarkers of pulmonology diseases, including BA, COPD, and ACOS.

Objective: This study aimed to investigate the expression level of free-circulating plasma microRNAs, hsa-miR-19b-3p, hsa-miR-125b-5p, and hsa-miR-320c in patients with BA, COPD and ACOS for the detection and validation of new microRNAs as biomarkers for chronic lung diseases.

Methods: The relative expression levels of 720 microRNAs were evaluated by Real Time-Polymerase Chain Reaction (RT-PCR) in patients with COPD and BA. Three upregulated microRNAs (hsa-miR-19b-3p, hsa-miR-125b-5p and hsa-miR-320c) were selected for further study. The obtained data were analyzed using the microRNA PCR Array Data Analysis tool. The sensitivity and specificity were estimated using the area under the Receiver Operating Characteristics curve (ROC).

Results: The expression level of free-circulating hsa-miR-19b-3p was decreased in the blood plasma of patients with BA and ACOS, and increased in patients with COPD. hsa-miR-125b-5p was downregulated in the blood plasma of patients with COPD and upregulated in patients with BA and ACOS. hsa-miR-320c was downregulated in the blood plasma of patients with BA, and upregulated in patients with COPD and ACOS. The ROC curves of patients with BA for hsa-miR-19b-3p, patients with ACOS for hsa-miR-125b-5p, and patients with COPD for hsa-miR-320c revealed the probability of them as valuable biomarkers with AUCs of 0.824, 0.825, and 0.855, respectively.

Conclusion: Our study revealed three promising biomarkers for the diagnosis of COPD, BA and ACOS.

Background: The prevalence of Cervical Cancer (CC) is disproportionately higher in developing countries. It is the second most frequent cancer type among Bangladeshi women and the major cause of morbidity and mortality. However, no previous data reported the association of miR-218-2 gene polymorphisms in Bangladeshi cervical cancer patients.

Aim: This case-control study was designed to find the link between the rs11134527 polymorphism in miR-218-2 and CC.

Methods: A total of 488 subjects were recruited, comprising 256 cervical cancer patients and 232 healthy females. Genotyping was conducted with the tetra-primer ARMS-PCR technique to detect the association.

Results: The results of genotype data showed that rs11134527 was in the Hardy-Weinberg equilibrium in both CC cases and controls (P >0.05). Overall, the polymorphism was found to be significantly associated with an increased risk of cervical cancer with AG genotype (AG vs. GG: OR = 2.26, 95% Cl = 1.40-3.66, P = 0.0008), AA genotype (AA vs. GG: OR = 3.64, 95% Cl = 2.17-6.10, P <0.0001), dominant model (AG+AA vs. GG: OR = 2.75, 95% Cl = 1.75-4.31, P <0.0001), recessive model (AA vs. GG+AG: OR = 2.08, 95% Cl = 1.41-3.08, P = 0.0002), and A allele (A vs. G: OR = 1.94, 95% Cl = 1.51-2.51, P <0.0001). All of these correlations remained statistically significant after performing Bonferroni correction (P <0.008).

Conclusion: Our study suggests that the rs11134527 polymorphism in the miR-218-2 gene contributes to the susceptibility of CC in Bangladeshi women.

Background: Endometrial cancer is one of the most common malignancies among women worldwide. Although this cancer is often diagnosed at early stages, the need for biomarkers of diagnosis remains a necessity to overcome conventional invasive procedures of diagnosis.

Objective: In our study, we aim to investigate the diagnostic value of microRNA-21 in endometrial cancer and its relation to clinicopathological features.

Methods: We used RT-qPCR to measure the expression of microRNA-21 in 71 tumor tissues, 53 adjacent tissues, and 54 benign lesions.

Results: Our results show that microRNA-21 is a potential biomarker for endometrial cancer with an area under the receiver operating characteristic curve of 0.925 (95% CI = 0.863 - 0.964, P<0.0001). The sensitivity was 84.51% (95% CI = 74.0 - 92.0) and specificity was 86.79% (95% CI = 74.7 - 94.5). For discrimination between benign lesions and controls the AUC was 0,881 with a sensitivity of 100% (95% CI = 93.4 - 100.0) and specificity of 66.04% (95% CI = 51.7 - 78.5), and for discriminating benign lesions from tumors the AUC was 0,750 with a sensitivity of 54.93% (95% CI = 42.7 - 66.8) and specificity of 90.74% (95% CI = 79.7 - 96.9). We also found that tumors with elevated microRNA-21 expression are of advanced FIGO stage, high histological grades, and have cervical invasion, myometrial invasion and distant metastasis.

Conclusion: Our findings support the important role of miR-21 as a biomarker to diagnose endometrial cancer. Further studies on minimally invasive/noninvasive samples such as serum, blood, and urine are necessary to provide a better alternative to current diagnosis methods.