microRNA Levels Research Articles

Anti-inflammatory effect of chlorogenic acid in Klebsiella pneumoniae-induced pneumonia by inactivating the p38MAPK pathway

IntroductionPneumonia is an inflammation-related respiratory infection and chlorogenic acid (CGA) possesses a wide variety of bioactive properties, such as anti-inflammation and anti-bacteria. AimThis study explored the anti-inflammatory mechanism of CGA in Klebsiella pneumoniae (Kp)-induced rats with severe pneumonia. MethodsThe pneumonia rat models were established by infection with Kp and treated with CGA. Survival rates, bacterial load, lung water content, and cell numbers in the bronchoalveolar lavage fluid were recorded, lung pathological changes were scored, and levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay. RLE6TN cells were infected with Kp and treated with CGA. The expression levels of microRNA (miR)-124–3p, p38, and mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) in lung tissues and RLE6TN cells were quantified by real-time quantitative polymerase chain reaction or Western blotting. The binding of miR-124–3p to p38 was validated by the dual-luciferase and RNA pull-down assays. In vitro, the functional rescue experiments were performed using miR-124–3p inhibitor or p38 agonist. ResultsKp-induced pneumonia rats presented high mortality, increased lung inflammatory infiltration and the release of inflammatory cytokines, and enhanced bacterial load, while CGA treatment improved rat survival rates and the above situations. CGA increased miR-124–3p expression, and miR-124–3p inhibited p38 expression and inactivated the p38MAPK pathway. Inhibition of miR-124–3p or activation of the p38MAPK pathway reversed the alleviative effect of CGA on pneumonia in vitro. ConclusionCGA upregulated miR-124–3p expression and inactivated the p38MAPK pathway to downregulate inflammatory levels, facilitating the recovery of Kp-induced pneumonia rats.

Oncolytic Measles Virus Encoding MicroRNA for Targeted RNA Interference.

Virotherapy is a promising, novel form of cancer immunotherapy currently being investigated in pre-clinical and clinical settings. While generally well-tolerated, the anti-tumor potency of oncolytic virus-based monotherapies needs to be improved further. One of the major factors limiting the replication efficiency of oncolytic viruses are the antiviral defense pathways activated by tumor cells. In this study, we have designed and validated a universal expression cassette for artificial microRNAs that can now be adapted to suppress genes of interest, including potential resistance factors. Transcripts are encoded as a primary microRNA for processing via the predominantly nuclear RNase III Drosha. We have engineered an oncolytic measles virus encoding this universal expression cassette for artificial microRNAs. Virally encoded microRNA was expressed in the range of endogenous microRNA transcripts and successfully mediated target protein suppression. However, absolute expression levels of mature microRNAs were limited when delivered by an oncolytic measles virus. We demonstrate that measles virus, in contrast to other cytosolic viruses, does not induce translocation of Drosha from the nucleus into the cytoplasm, potentially resulting in a limited processing efficiency of virus-derived, cytosolically delivered artificial microRNAs. To our knowledge, this is the first report demonstrating functional expression of microRNA from oncolytic measles viruses potentially enabling future targeted knockdown, for instance of antiviral factors specifically in tumor cells.

A rapid and simple method for simultaneous determination of three breast cancer related microRNAs based on magnetic nanoparticles modified with S9.6 antibody

Cancer progression is typically associated with the simultaneous changes of multiple microRNA (miR) levels. Therefore, simultaneous determination of multiple miR biomarkers exhibits great promise in early diagnosis of cancers. This research seeks to discuss a simple biosensing method for the ultrasensitive and specific detection of the three miRs related to the breast cancer based on S9.6 antibody coated magnetic beads, titanium phosphate nanospheres, and screen-printed carbon electrode. To prepare signaling probes, three hairpin DNAs (hDNAs) were labeled with three encoding titanium phosphate nanospheres with large quantities of different heavy metal ions (zinc, cadmium, lead), which have been utilized to discriminate the signals of three microRNA targets in relation with the corresponding heavy metal ions. After that, these hairpin structures hybridize with miR-21, miR-155 and miR-10b to form miR-21/hDNA1, miR-155/hDNA2 and miR-10b/hDNA3 complexes, which were captured by S9.6 antibodies (one anti-DNA/RNA antibody) pre-modified on magnetic bead surface. Therefore, the specific preconcentration of targets from complex matrixes can be carried out using magnetic actuation, increasing the sensitivity and specificity of the detection. The biosensor was suitably applied for direct and rapid detection of multiple microRNAs in real sample. It was observed that there were no significant differences between the results obtained by the suggested method and qRT-PCR as a reference method. So, this method makes an ultrasensitive novel platform for miRNAs expression profiling in clinical diagnosis and biomedical research.

Infant Saliva Levels of microRNA miR-151a-3p Are Associated with Risk for Neurodevelopmental Delay.

Prompt recognition of neurodevelopmental delay is critical for optimizing developmental trajectories. Currently, this is achieved with caregiver questionnaires whose sensitivity and specificity can be limited by socioeconomic and cultural factors. This prospective study of 121 term infants tested the hypothesis that microRNA measurement could aid early recognition of infants at risk for neurodevelopmental delay. Levels of four salivary microRNAs implicated in childhood autism (miR-125a-5p, miR-148a-5p, miR-151a-3p, miR-28-3p) were measured at 6 months of age, and compared between infants who displayed risk for neurodevelopmental delay at 18 months (n = 20) and peers with typical development (n = 101), based on clinical evaluation aided by the Survey of Wellbeing in Young Children (SWYC). Accuracy of microRNAs for predicting neurodevelopmental concerns at 18 months was compared to the clinical standard (9-month SWYC). Infants with neurodevelopmental concerns at 18 months displayed higher levels of miR-125a-5p (d = 0.30, p = 0.018, adj p = 0.049), miR-151a-3p (d = 0.30, p = 0.017, adj p = 0.048), and miR-28-3p (d = 0.31, p = 0.014, adj p = 0.048). Levels of miR-151a-3p were associated with an 18-month SWYC score (R = -0.19, p = 0.021) and probability of neurodevelopmental delay at 18 months (OR = 1.91, 95% CI, 1.14-3.19). Salivary levels of miR-151a-3p enhanced predictive accuracy for future neurodevelopmental delay (p = 0.010, X2 = 6.71, AUC = 0.71) compared to the 9-month SWYC score alone (OR = 0.56, 95% CI, 0.20-1.58, AUC = 0.567). This pilot study provides evidence that miR-151a-3p may aid the identification of infants at risk for neurodevelopmental delay. External validation of these findings is necessary.

Cigarette Smoke Enhances the Malignant Phenotype of Esophageal Adenocarcinoma Cells by Disrupting a Repressive Regulatory Interaction Between miR-145 and LOXL2

Although linked to esophageal carcinogenesis, the mechanisms by which cigarette smoke mediates initiation and progression of esophageal adenocarcinomas (EAC) have not been fully elucidated. In this study, immortalized esophageal epithelial cells and EAC cells (EACCs) were cultured with or without cigarette smoke condensate (CSC) under relevant exposure conditions. Endogenous levels of microRNA (miR)-145 and lysyl-likeoxidase 2 (LOXL2) were inversely correlated in EAC lines/tumors compared with that in immortalized cells/normal mucosa. The CSC repressed miR-145 and upregulated LOXL2 in immortalized esophageal epithelial cells and EACCs. Knockdown or constitutive overexpression of miR-145 activated or depleted LOXL2, respectively, which enhanced or reduced proliferation, invasion, and tumorigenicity of EACC, respectively. LOXL2 was identified as a novel target of miR-145 as well as a negative regulator of this miR in EAC lines/Barrett’s epithelia. Mechanistically, CSC induced recruitment of SP1 to the LOXL2 promoter; LOXL2 upregulation coincided with LOXL2 enrichment and concomitant reduction of H3K4me3 levels within the promoter of miR143HG (host gene for miR-145). Mithramycin downregulated LOXL2 and restored miR-145 expression in EACC and abrogated LOXL2-mediated repression of miR-145 by CSC. These findings implicate cigarette smoke in the pathogenesis of EAC and demonstrate that oncogenic miR-145-LOXL2 axis dysregulation is potentially druggable for the treatment and possible prevention of these malignancies.

Potential role of saffron and its components on miRNA levels in various disorders, a comprehensive review.

The potential therapeutic benefits of saffron and its active constituents have been investigated for the treatment of numerous illnesses. In this review, the impacts of saffron and its essential components on the levels of microRNAs (miRNAs) in different diseases have been delineated. Relevant articles were obtained through databases such as PubMed, Web of Sciences, Scopus, and Google Scholar up to the end of November 2022. miRNA expression has been altered by saffron and its active substances (crocin, crocetin, and safranal) which has been of great advantage in treating diseases such as cardiovascular, type 2 diabetes, cancers, gastrointestinal and liver disorders, central and peripheral nervous system disorders, asthma, osteoarthritis, ischemic-reperfusion induced injury conditions, and renal disorder. This study uncovered the potential restorative advantages of saffron and its derivatives, in miRNA imbalances in a variety of diseases.

Dysregulated MicroRNAs in the Pathogenesis of Systemic Lupus Erythematosus: A Comprehensive Review.

Systemic lupus erythematosus is a chronic autoimmune disease of which clinical presentation is vastly heterogeneous, ranging from mild skin rashes to severe renal diseases. Treatment goal of this illness is to minimize disease activity and prevent further organ damage. In recent years, much research has been done on the epigenetic aspects of SLE pathogenesis, for among the various factors known to contribute to the pathogenic process, epigenetic factors, especially microRNAs, bear the most therapeutic potential that can be altered unlike congenital genetic factors. This article reviews and updates what has been discovered so far about the pathogenesis of lupus, while focusing on the dysregulation of microRNAs in lupus patients in comparison to healthy controls along with the potentially pathogenic roles of the microRNAs commonly reported to be either upregulated or downregulated. Furthermore, this review includes microRNAs of which results are controversial, suggesting possible explanations for such discrepancies and directions for future research. Moreover, we aimed to emphasize the point that had been overlooked so far in studies regarding microRNA expression levels; that is, which specimen was used to assess the dysregulation of microRNAs. To our surprise, a vast number of studies have not considered this factor and have analyzed the potential role of microRNAs in general. Despite extensive investigations done on microRNA levels, their significance and potential role remain a mystery, which calls for further studies on this particular subject in regard of which specimen is used for assessment.

MicroRNAs in aldosterone production and action.

Aldosterone is a cardiovascular hormone with a key role in blood pressure regulation, among other processes, mediated through its targeting of the mineralocorticoid receptor in the renal tubule and selected other tissues. Its secretion from the adrenal gland is a highly controlled process subject to regulatory influence from the renin-angiotensin system and the hypothalamic-pituitary-adrenal axis. MicroRNAs are small endogenous non-coding RNA molecules capable of regulating gene expression post-transcriptionally through stimulation of mRNA degradation or suppression of translation. Several studies have now identified that microRNA levels are changed in cases of aldosterone dysregulation and that microRNAs are capable of regulating the expression of various genes involved in aldosterone production and action. In this article we summarise the major studies concerning this topic. We also discuss the potential role for circulating microRNAs as diagnostic biomarkers for primary aldosteronism, a highly treatable form of secondary hypertension, which would be highly desirable given the current underdiagnosis of this condition.

Postgenomic and structural changes in the myocardia of Wistar rats fed a high-salt diet

The relationship between dietary sodium, hypertension, and cardiovascular injury is far from clear. One of the important links in this process can be microRNAs that have the ability to modulate gene expression at the post-transcriptional level. However, their role in this process has not been fully studied. In addition, further studies require the identification of structural changes in the myocardium in conditions of long-term consumption of a high-salt diet. The aim of the study was to evaluate the expression levels of nuclear transcription factor κB (NFκB), microRNA (miRNA)-21 and structural changes in the myocardium during long-term consumption of a diet containing 8% (high) sodium chloride in Wistar rats. Material and methods. 20 Wistar rats with initial body weight 280.5±42.7 g were divided into two equal groups. The high salt (HS) group received 8% NaCl in the diet, the control (NS) group received the standard diet (0.34% NaCl). After 4 months, systolic blood pressure was measured in rats using the cuff method on the tail; the myocardial mass index was assessed after dissection; histological and electron microscopic examination of the myocardium was performed, and the expression levels of miRNA-21 and NFκB in the myocardium were determined. Results and discussion. Consumption of a diet high in sodium chloride for 4 months did not significantly affect the level of systolic blood pressure in normotensive Wistar rats, but led to an increase in myocardial mass index by 25.0% (p<0.05). In the HS group, hypertrophy of cardiomyocytes and an increase in the wall thickness of arterial vessels were revealed. The area of perivascular fibrosis in rats of the HS-group was almost 1.8 fold higher than in the NS-group. In animals of HS-group, the relative levels of expression of NFκB (more than 2 times) and miRNA-21 (almost 6 times) increased compared with the control. It can be assumed that the negative impact on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and miRNA-21 activation. Conclusion. In Wistar rats, long-term use of a high-salt diet results in myocardial remodeling that is not associated with changes in blood pressure. At the same time, the adverse effects of high salt intake on the myocardium are mediated, in particular, by postgenomic mechanisms, namely an increase in the expression levels of NFκB and microRNA-21.

EXPRESSION LEVELS OF FOXO-1, P27KIP1, MIR-27, MIR-186 AND AKT1/AKT-P PROTEINS IN WOMEN WITH ENDOMETRIAL CANCER AND HYPERPLASIA: IMPLICATIONS FOR THE HUMAN REPRODUCTIVE SYSTEM.

Despite extensive research on endometrial cancer (EC) and endometrial hyperplasia, there is still a gap in understanding the molecular mechanisms underlying their development and progression. The aim of this study was to investigate the expression levels of FOXO-1, P27Kip1, miR-27, and miR-186, and Akt1, Akt-P proteins in patients with EC and endometrial hyperplasia compared to control subjects. Samples of the endometrial tumor (n=30), normal (control) (n=30) and endometrial hyperplastic (n=30) tissue were obtained from patients referring to Arash and Imam Khomani hospitals, Tehran, Iran. Expression levels of genes and microRNAs were evaluated by qRT- PCR. Western blot analysis was applied for protein evaluation. The data were analyzed using t-test, Mann -Whitney U, Pearson correlation coefficient analysis, ANCOVA and ANOVA. There was significant decrease in FOXO-1 in EC tissue compared to control tissue (p<0.05). Significant increase was observed in expression of miR-27 in patients with EC (p<0.001) and hyperplasia (p<0.01), whereas miR-186 expression level increased significantly only in patients with EC (p<0.05). P27Kip1 expression level did not significantly change in patients with EC and hyperplasia. There was a significant association between expression levels of miR-27 with FOXO-1 and P27Kip1 in patients with EC. Western blot analysis revealed higher endometrial AKT1-P protein levels in patients with EC and hyperplasia than control subjects (p<0.05). Our findings suggest that FOXO-1, miR-27, miR-186, and Akt1-P/Akt1 protein have the potential to serve as tissue biomarkers for early diagnosis, prognosis, and progression of EC in the human reproductive system.

Serum miR-181a and miR-25 in patients with malignant and benign breast diseases.

Breast tumor diseases include a wide range of pathologies that require different approaches to their treatment. MicroRNA (miR) levels, reflecting regulation of the gene expression involved in tumorigenesis, can be diagnostic and prognostic markers of breast diseases. The levels of circulating miR-181a and miR-25 were measured in patients with benign breast diseases (BBD), patients with invasive carcinoma of a nonspecific type (ICNT) and also in conditionally healthy women. Expression of both miRs was higher in patients of both groups as compared to controls; at the same time, the content of serum miR-181a and miR-25 was higher in BBD patients than in ICNT patients. The detected changes may be of interest in the context of precancerous changes in BBD. It seems possible to use them in the future as markers of the pathological process as a part of a large diagnostic panel.

ПОРАЖЕНИЕ КОРОНАРНОГО РУСЛА, БИОЛОГИЧЕСКИЙ ВОЗРАСТ И УРОВЕНЬ МИКРО-РНК У БОЛЬНЫХ СТАБИЛЬНОЙ ИБС С ПОГРАНИЧНЫМИ СТЕНОЗАМИ КОРОНАРНЫХ АРТЕРИЙ

Objective. To compare the nature of coronary vascular bed lesion, vascular wall stiffness depending on passport and biological and age ratio, and to study microRNA (miRNA) levels in different clinical phenotypes stable coronary artery disease (CAD) (pt) with borderline coronary artery (CA) stenosis. Material and methods. 258 stable angina 1-3 class patients (51 - 19.8% women and 207 - 80.2% men) with borderline CA stenosis and the presence of hypertension were included in the comparative descriptive trial of three parallel groups. All pts along with clinical examination and ultrasound of the heart underwent selective coronary angiography. The passport and biological age ratio were evaluated using a VaSera VS-1500N. Determination of miRNA levels was carried out using the PCR method in real time. Statistical calculations were carried out using the RStudio program (version 2022.07.2+576, USA) and the R language (version 4.1.3 (2022-03-10), Austria). Results. One with the CAD phenotype without diabetes mellitus (DM) and obesity (n=115 (44.6%)), the CAD phenotype with type 2 (n = 55 (21.3%)) and CAD with metabolically unfavorable obesity phenotype (MUOP) ([n=88 (34.1%)) prevailed among PTs with borderline CA stenosis when conducting a random sample. The features of the coronary vascular bed lesion are stenosis of the anterior descending artery and the circumflex artery especially in the distal segments in CAD and DM pts. The frequency of the right CA lesion was higher in CAD with the MUOP phenotype, also with more pronounced distal segments. Pts with biological age predominance are characterized by an unborable course of the disease, as a well as cardiometabolic profile. MiRNA concentration assessment revealed increased miRNA-221 levels in CAD with MUOP pts and increased miRNA-22 and -126 levels in CAD and DM pts. Conclusion. Stable patients with CAD with borderline CA stenosis represent a serious condition in prognostic terms due to a long history of hypertension and expressed cardiometabolic associations and a frequent increase in biological age. The assessment of the miRNA levels of these pts is of great interest and represents a promising direction for use in diagnosis and treatment.

Discordant immune response among treatment experienced patients infected with HIV-1: Crosstalk between MiRNAs expression and CD4+ T cells count.

One of the problems with treating HIV-infected patients with ARVs is that the treatment can reduce viral load and does not increase the number of CD4 cells (immunological discordance). There are still challenges to treating HIV-positive patients. This study aimed to investigate the expression level of 18 miRNAs involved in the proliferation and differentiation of CD4+ T cells in a target (discordant immune response) and a control (immune response) group. In this case-control study, 18 miRNAs were selected and synthesized according to the in-silico analysis and published literatures. RNA extraction was performed from PBMC cells of 30 HIV-1 positive patients in the sample bank. The expression level of microRNAs was calculated by the relative q PCR method (2-ΔΔCt method), and data were analyzed using GraphPad Prism software version 8.0.2. The results of fold change calculation and statistical analysis showed that the expression levels of miR-30b (p value: 0.01, fold change: 0.23), miR-155 (p value: 0.04, fold change: 0.44), miR-181a (p value: 0.01, fold change: 0.37), and miR-190b (p value: 0.01, fold change: 0.39) had a significant decrease in the target group compared to the control group. In summary, various studies have shown that miRNAs, including miR-30b, miR-155, miR-181a, and miR-190b, are involved in the proliferation, differentiation, and development of CD4+ T cells. One reason for the lack of increase in CD4+ T cells may be the reduced expression of these miRNAs.

Expression Levels of MicroRNA-300/BCL2L11 in Papillary Thyroid Cancer and Their Clinical Diagnostic Values

Introduction: This research aims to explore the expression levels of microRNA (miRNA)-300/BCL-2-like protein 11 (BCL2L11) and their values in the clinical diagnosis of papillary thyroid cancer (PTC). Methods: Pathological tissues that were surgically removed for thyroid disease were selected. miR-300 and BCL2L11 expression levels in the samples were measured. Receiver operating characteristic (ROC) curves were plotted to analyze miR-300 and BCL2L11 predictive values for PTC. Upon silencing miR-300 and silencing BCL2L11 in PTC cells, the corresponding miR-300 and BCL2L11 expression levels were tested, followed by examining PTC cell activities. The targeting relationship of miR-300 and BCL2L11 was detected by the bioinformatics website and luciferase activity assay. Results: miR-300 expression levels were elevated and BCL2L11 expression levels were reduced in PTC tissues. miR-300 and BCL2L11 expression levels in PTC tissues had a correlation with TNM stage and lymph node metastasis. The results of ROC curve revealed that both miR-300 and BCL2L11 had clinical predictive values for PTC. Mechanistically, miR-300 negatively regulated BCL2L11. The functional assays unveiled that silencing miR-300 impeded PTC cell activities, and silencing BCL2L11 induced PTC cell activities. In the rescue experiment, silencing BCL2L11 reversed the impacts of silencing miR-300 on PTC cell development. Conclusion: This study underlines that miR-300 expression is increased and BCL2L11 expression is declined in PTC. miR-300 and BCL2L11 both have clinical predictive values for diagnosing PTC.

Association between Diagnostic microRNAs of Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Meta-Analysis

Non-alcoholic fatty liver disease is a high-risk factor for the morbidity and mortality of type 2 diabetes mellitus. Thus, we conducted a meta-analysis to investigate whether the microRNAs associated with non-alcoholic fatty liver disease are associated with diabetes and their potential to predict diabetes in non-alcoholic fatty liver disease individuals. We conducted a systematic literature search using PubMed, Cochrane library and Embase databases. The literature about circulating microRNA levels in nonalcoholic fatty liver disease individuals was screened according to the inclusion and exclusion criteria. The sensitivity, specificity and area under curve of different microRNAs were summarized. These microRNAs with higher diagnostic efficacy and stability were selected for further analysis in people with diabetes. In all, 10 of 1950 studies determining microRNA expression profiles in non-alcoholic fatty liver disease were included in the final analysis. Using area under curve ≥0.7 as the criterion, we screened out 10 microRNAs that have moderate diagnostic efficacy in non-alcoholic fatty liver disease, including microRNA-122, microRNN-34a, microRNA-99a, microRNA-16, microRNA-379, microRNA-197, microRNA-181d, microRNA-146b, microRNA-375 and microRNA-12. The pooled area under curve of microRNA-122 and microRNA-34a in the diagnosis of non-alcoholic fatty liver disease was 0.88 (95 % confidence interval: 0.81–0.96) and 0.86 (95 % confidence interval: 0.82–0.91), respectively. Further, 30 of 2674 studies related to diabetes and the above microRNA were included in the final analysis. The results showed that microRNA-122 and microRNA-34a showed higher stability in non-alcoholic fatty liver disease and diabetes. In conclusion, microRNA-122 and microRNA-34a are common biomarkers of both non-alcoholic fatty liver disease and type 2 diabetes mellitus. However, whether they can be used as effective biomarkers for the early prediction of diabetes in patients with non-alcoholic fatty liver disease lacks valid evidence.

Plasma microRNAs levels associate with the outcome of ARDS patients

Background: Mesenchymal stem cells (MSC) are stromal cells with renew ability for multilineage differentiation. Therefore MSC has been considered as a therapy method for rebuilding alveoli structure and repairing the function of pulmonary vascular endothelial cells (VEC). However, whether MSC can play a therapeutic role in ARDS patients depends on different ARDS phenotypes. Recent studies about microRNAs (miRNAs) proved that miRNAs played important roles in MSC regulating function and activity of VEC which may affect therapeutic response and outcome to different ARDS patients, but few studies focused on this field. The purpose of our study is that plasma miRNAs regulated VEC’s function and specific miRNAs which were related to MSC and VEC (MSC‑VEC‑miRNAs) expressed differently between survival and non-survival ARDS patients. We aim to find specific MSC‑VEC‑miRNAs which are associated with the outcome of ARDS patients. Methods: We obtained MSC-VEC-miRNAs through searching PUBMED database. A number of 101 ARDS patients were screened and 57 of them were included in our research within 24 hours of admission to ICU. We then collected their clinical data and their blood samples, then we did real-time PCR to test plasma levels of MSC-VEC-miRNAs. Results: Fourteen MSC-VEC-miRNAs were selected in this study. We included 57 ARDS patients and 18(31.6%) of them died on Day 28 after diagnosis. Plasma miR-26a level in non-survival group was significantly lower than that in survival group (0.33[0.09-1.17] vs. 0.97[0.17-3.49], P=0.046). Plasma miR-320 level in non-survival group was significantly higher than that in survival group (0.37[0.16-1.66] vs. 0.18[0.07-0.39], P=0.041). There was no statistical difference of other 12 miRNA between two groups. Conclusion: Plasma miR-26a and miR-320 levels have a certain predictive value for the prognosis of ARDS patients.

Investigation of the expression levels of miR-21, miR-132, miR-29a, miR-204, and miR-138 in patient's plasma with primary OSCCs

This is the eighth most malignant tumor in the world, causing the highest incidence and malignancy rate of all cancers in the mouth and maxillofacial region. In cells, miRNAs regulate development, differentiation, proliferation, and differentiation, and miRNA expression is a better indicator of physiological status than DNA expression. miR-21, miR-132, miR-29a, miR-204, and miR-138 levels were measured in plasma from patients with primary OSCC and healthy controls. A Real Time-PCR technique was used to measure miR-21, miR-132, miR-29a, miR-29a, and miR-204 expression levels in plasma from 38 healthy and 38 people with primary OSCC. A standard distribution test and a CT unit were used to confirm the quantitative data on miRNA expression. Gene expression levels were compared between two groups of patients and healthy groups using a Mann-Whitney test and an unpaired t-test. MiR-21's median CT value was 29.68 in the OSCC group and 32.89 in the healthy group, and miR-29a's median CT value was 37.54 and 36.46 in the OSCC group and healthy group, respectively. Additionally, miR-132's CT values were 37.71 and 36.40, miR-138's CT value was 35.37 and 31.21, and miR-204's CT value was 36.44 and 36.17. The results showed that miR-21 expression levels increased significantly, while miR-29a, miR-132, and miR-138 (P < 0.05), and miR-204 expression levels did not differ significantly (P > 0.05). As a result of this study, the expression levels of microRNAs may be considered to diagnose OSCC at an early stage. It is essential to diagnose this disease early to improve treatment and patient health outcomes.

LncRNA MIAT Upregulates NEGR1 by Competing for miR-150-5p as a Competitive Endogenous RNA in SCIRI Rats.

Spinal cord ischemia-reperfusion injury (SCIRI) can cause a pathological state of irreversible delayed death of neurons in the spinal cord tissue and a range of complications, such as spinal cord dysfunction and motor function impairment. This study aimed to determine whether the long-stranded non-coding ribonucleic acid (lncRNA), myocardial infarction-associated transcript (MIAT), could upregulate neuronal growth regulator 1 (NEGR1) by competing for miR-150-5p as a competitive endogenous RNA in a rat SCIRI model. The MIAT knockdown vector or the corresponding blank vector was injected into the spinal cord of healthy sprague Dawley (SD) rats. Administration of the MIAT knockdown vector led to the establishment of the SCIRI rat model. Basso, Beattie & Bresnahan locomotor rating scale (BBB) assessment of hind limb motion. Pathological changes in the spinal cord were observed via hematoxylin and eosin staining and eosin staining. Quantitative polymerase chain reaction was performed to determine the expression levels of the candidate microRNAs and predicted candidate genes, and the relationship between them. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining was used to detect apoptosis in the spinal cord tissue of rats in each group. Western blotting was performed to determine the expression of the apoptosis-related proteins, caspase-9, caspase-3, and BCL2-Associated X (Bax)/B-cell lymphoma-2 (Bcl-2). The luciferase reporter gene was used to assess the interaction among the lncRNA, MIAT, and miR-150-5, and the interaction between miR-150-5 and NEGR1. The sh-lncRNA, MIAT, improved exercise status, and pathological changes in the spinal cord of SCIRI rats, inhibited apoptosis, increased the expression of miR-150-5p, and reduced the expression of NEGR1. Compared with mimics-NC, the transfection of miR-150-5p significantly decreased the relative fluorescence activity ratio of MIAT 3'-untranslated region (3'-UTR) wild-type Human embryonic kidney cells 293 (HEK-293 cells). Compared with mimics-negative control (NC), the transfection of miR-150-5p significantly decreased the relative fluorescence activity ratio of NEGR1 3'-UTR wild-type HEK-293 cells. MIAT can affect the symptoms of SCIRI in rats. Furthermore, as a competitive endogenous RNA, MIAT upregulates NEGR1 by competing with miR-150-5p in SCIRI rats.

Plasma microRNA-192-5p can predict the response to neoadjuvant chemotherapy and prognosis in esophageal cancer.

Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. Recently, neoadjuvant chemotherapy (NAC) before curative surgery has become a standard treatment for clinical stage II or III EC patients. Some EC patients receive a complete response (CR) by NAC; thus, curative surgery may be unnecessary for such patients. MicroRNA levels in plasma have the potential to be a predictor of response to NAC. In the present study, we focused on miR-192-5p, which is highly expressed in EC tissue. The purpose was to investigate the correlations between levels of plasma miR-192-5p and the response to NAC. Furthermore, molecular functions of miR-192-5p associated with chemosensitivity were examined using EC cell lines. The levels of miR-192-5p in plasma before surgery were evaluated in 113 EC patients. Sixty-nine patients received NAC. miR-192-5p levels in the CR group were significantly higher than in the other groups (p=0.002). The downregulation of miR-192-5p in the EC cell line inhibited sensitivity to cisplatin, and the overexpression of miR-192-5p in the EC cell line promoted sensitivity to cisplatin. miR-192-5p regulated sensitivity to cisplatin by targeting ERCC3 and ERCC4. Plasma miR-192-5p could be used as a predictor of response to chemotherapy and prognosis in EC patients.

METTL3 is aberrantly expressed in endometriosis and suppresses proliferation, invasion, and migration of endometrial stromal cells.

Endometriosis (EM) is one of the leading gynecological disorders, and associated with excessive functioning of endometrial stromal cells (ESCs). The current study was conducted to determine the expression and role of methyltransferase-like 3 (METTL3) in the proliferation, invasion, and migration of ESCs in EM. The documented expression levels of METTL3, microRNA (miR)-21-5p, and WNT inhibitory factor 1 (WIF1) in eutopic (Eut) and ectopic (Ect) endometrial tissues and ESCs were determined by a combination of real-time quantitative polymerase chain reaction and Western blot assay. After transfection with pcDNA3.1-METTL3, miR-21-5p mimic, and WIF1 small interfering RNA, cell counting kit-8, colony formation, and Transwell assays were performed in the Ect ESCs (Ect-ESCs). Subsequently, the binding of miR-21-5p to METTL3 was analyzed, along with quantification of the N6-methyladenosine (m6A) level, the enrichments of METTL3 and m6A on WIF1, and the mRNA stability of WIF1. In our findings, METTL3 was downregulated in the EM tissues and cells. METTL3 overexpression intrinsically reduced the proliferation, invasion, and migration of Ect-ESCs. miR-21-5p inhibited the METTL3 expression while METTL3 enhanced the mRNA stability and expression of WIF1 via m6A modification. Additionally, a negative correlation of METTL3 was identified with miR-21-5p along with a positive correlation with the WIF1 mRNA in EM tissues. The miR-21-5p overexpression or WIF1 downregulation enhanced the proliferation, invasion, and migration of Ect-ESCs. Collectively, miR-21-5p inhibited the METTL3-mediated m6A modification and mRNA stability of WIF1, thereby facilitating the proliferation, invasion, and migration of Ect-ESCs.