LncRNA NEAT1 and miRNA 101 as potential diagnostic biomarkers in patients with alopecia areata.

Background: Alopecia areata (AA) commonly displays as non-scarring, irregular hair loss. Experimental and clinical research have specifically implicated autoimmunity and genetics in the disruption of anagen hair follicles. AA patients' scalp lesions and peripheral blood mononuclear cells (PBMCs) exhibited an immune state imbalance. Numerous studies attempt to establish a connection between the occurrence and prognosis of AA and the epigenetic modulation of gene expression by long noncoding RNA (lncRNA) and microRNA (miRNA). The current study aimed to examine the serum levels of nuclear enriched abundant transcript 1 (NEAT1) and its target miRNA101 (miR-101) in AA and investigate the ability to use them as diagnostic biomarkers in the disease. Methods: Seventy-two AA patients were included in this prospective cohort study. Demographics, patient history, laboratory characteristics, and treatments were recorded. The miR-101 and NEAT1 levels were evaluated. Results: Serum NEAT1 levels were lower in AA patients, but there was no significant difference. However, there was no substantial disparity in NEAT1 level regarding other disease characteristics. There was a substantial positive association between NEAT1 and miR-101 levels among cases. On the other hand, the results showed a markedly low mean of miR-101 levels among patients, but the miR-101 marker shows no significant difference regarding different disease characteristics. The specificity and sensitivity test for the miR-101 marker shows a significant specificity of 60 % and sensitivity of 75 % with a p-value of 0.001 and a cut-off value of 0.897. Conclusions: The current research determined that miR-101 works as a diagnostic biomarker for AA.

MiR-6721-5p as a natural regulator of Meta-VCL is upregulated in the serum of patients with coronary artery disease.

Background: Coronary artery disease (CAD), the leading cause of mortality globally, arises from atherosclerotic blockage of the coronary arteries. Meta-vinculin (meta-VCL), a large spliced isoform of VCL, co-localizes in muscular adhesive structures and plays significant roles in cardiac physiology and pathophysiology. This study aimed to identify microRNAs (miRNAs) regulating meta-VCL expression and investigate the expression alterations of the miRNAs of interest and meta-VCL as potential biomarkers in the serum of CAD patients. Methods: Bioinformatics tools were employed to select miRNAs targeting meta-VCL. Cell-based ectopic expression analysis and a dual-luciferase assay were used to examine the interactions between miRNAs and meta-VCL. An ELISA assessed the concentrations of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α). MiRNA and meta-VCL expression patterns and biomarker suitability were evaluated in serum samples from CAD and non-CAD individuals using real-time PCR. A cardiac cell-line data set and CAD blood exosome samples were analyzed using bioinformatics and ROC curve analyses, respectively. Results: miR-6721-5p directly interacted with the putative target sites at the 3'-UTR of meta-VCL and regulated its expression. IL-10 and TNF-α concentrations, which may act as anti-inflammatory factors, decreased following miR-6721-5p upregulation and meta-VCL downregulation. Bioinformatics and experimental expression analyses confirmed downregulated meta-VCL expression and upregulated miR-6721-5p expression in CAD samples. ROC curve analysis yielded an AUC score of 0.705 (P = 0.018), indicating the potential suitability of miR-6721-5p as a biomarker for CAD. Conclusions: miR-6721-5p plays a regulatory role in meta-VCL expression and may contribute to CAD development by reducing anti-inflammatory factors. These findings suggest that miR-6721-5p could serve as a novel biomarker in the pathogenesis of CAD.

ADAR1-regulated miR-142-3p/RIG-I axis suppresses antitumor immunity in nasopharyngeal carcinoma.

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

MiR-204-5p overexpression abrogates Dacarbazine-induced senescence in melanoma cells in vivo MiR-204-5p abrogates senescence.

Cancer cell drug resistance hinders significantly therapeutic modalities in oncology. Dacarbazine is chemotherapeutic agent traditionally used for melanoma treatment although it's effectiveness insufficient. In the present study we performed NGS-based transcriptomic profiling of B16 melanoma tumors after Dacarbazine treatment in vivo. Whole transcriptome sequencing revealed 34 differentially expressed genes most of them associated with drug resistance and apoptosis evading. In accordance to bionformatic analysis, 6 signaling cascades: "D-Amino acid metabolism", "NF-kappa B signaling pathway", "Phosphatidylinositol signaling system", "P53 signaling pathway", "IL-17 signaling pathway" and "Bile secretion" were enriched by differentially expressed genes. Next we provided a combined treatment by Dacarbazine and miR-204-5p mimic as miR-204-5p was considered previously implicated in cancer drug resistance. This approach lead to an increase of miR-204-5p expression in B16 melanoma cells in vivo that was accompanied by subsequent decrease in the expression of miR-204-5p target genes - BCL2 and SIRT1 in the primary tumors. MiR-204-5p overexpression with Dacarbazine application resulted in increased the weight, and volume of primary tumors and diminished the proportion of ß-Galactosidase expression in melanoma B16-bearing mice. Taking together, our study revealed that although miR-204-5p showed antiproliferative capacities in vitro, it's mimic in combination with Dacarbazine is able to potentiate tumor growth triggering probably a switch from senescent to proliferative phenotype of malignant cells.

The Interplay between MiR-134/BDNF and LKB1/AMPK/SIRT1 Accentuates the Antidepressant Efficacy of Empagliflozin in Ovariectomized Rats.

Major depressive disorder (MDD) is considered a major cause of suicide worldwide. As previous studies revealed that neuroinflammation is a significant factor in the etiology of MDD, this study proposed to unravel the possible antidepressant effect of Empagliflozin (EMPA) through targeting miRNA-134 (miR-134)/brain-derived neurotrophic factor (BDNF) and liver kinase B1 (LKB1)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) axes in ovariectomized (OVX) female rats. Rats were assigned randomly to four groups: Sham operation (SO), OVX, OVX + EMPA (10 mg/kg/day, p.o.), and OVX + EMPA + Dorsomorphin (DORSO) (25 µg/day/rat, i.v.). Drugs were administered for 28 days after 2 weeks of surgery. EMPA debilitated OVX-induced depressive-like behavior by mitigating the immobility time in the tail suspension test and forced swimming test. Moreover, EMPA curtailed OVX-induced alterations of serum estradiol, hippocampal serotonin, miR-134 expression, as well as BDNF. EMPA also dwindled OVX-induced changes of hippocampal p-LKB1/LKB1, p-AMPK/AMPK, SIRT1, and inflammatory markers (nuclear factor-kappa-B, interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha). Additionally, the EMPA-treated group exhibited marked improvement in different brain regions' histopathology. However, DORSO coadministration reversed most of EMPA's beneficial effects. The current study displayed the modulatory role of EMPA on miR-134/BDNF and LKB1/AMPK/SIRT1 axes, thus offering a partial explanation of its antidepressant efficacy and proposing EMPA as a novel therapeutic avenue for MDD.

LncRNA-SNHG16 Protects Against Oxidative Stress-Induced Vascular Endothelial Cell Injury in Cardiovascular Diseases by Regulating the miR-23a-3p-GLS-Glutamine Metabolism Axis.

Cardiovascular diseases are disorders of the heart and vascular system that cause high mortality rates worldwide. Vascular endothelial cell (VEC) injury caused by oxidative stress (OS) is an important event in the development of various cardiovascular diseases, including ischemic heart disease. This study aimed to investigate the critical roles and molecular mechanisms of long non-coding RNA (lncRNA) SNHG16 in regulating vascular endothelial cell injury under oxidative stress. We demonstrated that SNHG16 was significantly downregulated and miRNA-23a-3p was notably induced in human vascular endothelial cells under OS. Overexpressing SNHG16 or silencing miR-23a-3p effectively mitigated the OS-induced VEC injury. Additionally, glutamine metabolism of VECs was suppressed under OS. SNHG16 protected the OS-suppressed glutamine metabolism, while miR-23a-3p functioned oppositely in VECs. Furthermore, SNHG16 downregulated miR-23a-3p by sponging miR-23a-3p, which direct targeted the glutamine metabolism enzyme, GLS. Finally, restoring miR-23a-3p in SNHG16-overexpressing VECs successfully reversed the protective effect of SNHG16 on vascular endothelial cell injury under OS. In summary, our results revealed the roles and molecular mechanisms of the SNHG16-mediated protection against VEC injury under OS by modulating the miR-23a-3p-GLS pathway.

Adipose tissue-derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity.

INTRODUCTION: Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited. OBJECTIVES: To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA. METHODS: The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo. RESULTS: Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (Ggpps) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process . CONCLUSIONS: Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad-EVs and the miR-3074-5p may represent a promising therapeutic strategy for obesity-related TMJ OA. KEY POINTS: High-fat-diet-induced obesity aggravate the progression of TMJ OA in mice. Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles. Inhibition of miR-3074-5p/SMAD4 pathway in chondrocyte alleviated the effect of HFD-EVs on TMJ OA.

Alleviative effects of green-fabricated zinc oxide nanoparticles on acrylamide-induced oxidative and inflammatory reactions in the rat stomach via modulating gastric neuroactive substances and the MiR-27a-5p/ROS/NF-κB axis.

Little is known about the effects of acrylamide (AMD) on the stomach. So, this study evaluated the effect of oral AMD exposure (20 mg/kg b.wt) on oxidative status, apoptotic, and inflammatory reactions in rat's stomach for 60 days. To explore novel targets of AMD toxicity, a more detailed molecular and immune-expression study was performed. Besides, the possible protective effect of green synthesized zinc oxide nanoparticles (G-ZNP) (10 mg/kg b.wt) was explored. The results revealed that AMD significantly provoked oxidative and lipid peroxidative damage of the stomach in terms of increased ROS and MDA but reduced SOD, CAT, GSH, and GSH/GSSG. Additionally, the stomachs of AMD-exposed rats showed a significant increment of PGE2 but reduced NO. Histopathologically, AMD induced a significant increase in PAS stain and the immunoexpression of iNOS and NF-κB in the glandular stomach. A significant upregulation of CART, VACHT, EGFR, caspase-3, NOS-1, and miR-27a-5p was evident in the stomach of the AMD group. Yet, G-ZNP oral dosing significantly rescued the AMD-induced oxidative damage, apoptotic reaction, inflammatory effect, and altered miR-27a-5p and gene expressions in the stomach. Conclusively, these findings demonstrated the efficacy of G-ZNP in protecting against the harmful impacts of acrylamide on stomach tissues.

The study on the mechanism of miR-29a in SPPV infection.

The members of the miR-29 family play an important role in the process of viral infection. The sheep pox epidemic has hindered the development of the livestock industry worldwide. The aim of this study was to analyze the action mechanism of miR-29a during sheep pox virus (SPPV) infection. We found that during viral infection, miR-29a showed a trend of increasing, then decreasing, and then again increasing. It was determined that AKT3 was a target gene of miR-29a, and miR-29a might be involved in the PI3K-AKT signaling pathway. SPPV was able to inhibit cell proliferation and promote apoptosis, and miR-29a reversed the inhibition of cell proliferation by SPPV and the promotion of apoptosis. This study provides an experimental basis and theoretical foundation for the pathogenic mechanism of SPPV infection, as well as contributing to the proposal of new strategies for the development of anti-sheep-poxvirus drugs.

Expressing miR-282 mitigates Aß42-induced neurodegeneration in Alzheimer's model in Drosophila.

Alzheimer's disease is a complex neurodegenerative condition characterized by the accumulation of amyloid beta plaques, leading to memory loss, cognitive decline, and impaired autonomous behavior. Despite extensive research, an effective treatment remains elusive. The buildup of amyloid beta plaques (Aß42) in the brain causes oxidative stress and disrupts normal molecular signaling, adversely affecting neuron function. Previous research has identified factors that can either exacerbate or mitigate neurodegenerative diseases. Our study aimed to uncover new factors involved in the pathogenesis of Alzheimer's disease. Using Drosophila as a model organism, we employed the Gal4/UAS system to express human Aß42 in the flies' retinal neurons which led to neurodegenerative changes in their compound eyes. To identify genetic modifiers, we conducted a screen by co-expressing microRNAs and found that miR-282 acts as a suppressor. Overexpressing miR-282 in the GMR > Aß42 background reduced Aß42-induced neurodegeneration. Further analysis using prediction tools and RNA interference experiments identified three potential downstream targets of miR-282: calpain-B, knot, and scabrous. Downregulating these genes via RNA interference in the GMR > Aß42 background mitigated neurodegeneration. Our research highlights miR-282 as a novel molecule that may influence the progression of Alzheimer's disease, offering potential avenues for future therapeutic or diagnostic developments.

Bone marrow mesenchymal stem cells-derived exosomal miR-381 alleviates lung ischemia-reperfusion injury by activating Treg differentiation through inhibiting YTHDF1 expression.

AIM: Our study aimed to investigate whether BMSCs-derived exosomal miR-381 promotes Treg cell differentiation in lung ischemia-reperfusion injury (LIRI), and the underlying mechanism. METHODS: The in vitro and in vivo models of LIRI were established by hypoxia/reoxygenation (H/R) treatment and lung ischemia/reperfusion (I/R) surgery, respectively. BMSCs-derived exosomes were isolated and identified by western blot, nanoparticle tracking analysis, and transmission electron microscopy. Cell viability, proliferation, and apoptosis were assessed by CCK-8, EdU, and flow cytometry assay, respectively. IL-18 secretion level in lung microvascular endothelial cells (LMECs) and lung tissue homogenate was examined by ELISA. Treg cell differentiation was determined using flow cytometry. The relationships between miR-381, YTHDF1, and IL-18 were investigated using dual-luciferase reporter gene, RIP, and/or RNA pull-down assays. MeRIP assay was employed to determine m6A modification of IL-18 mRNA in LMECs. The ubiquitination level of Foxp3 protein in CD4+ T cells was analyzed by Co-IP assay. RESULTS: BMSCs-derived exosomes reduced LMECs injury and increased Treg cell differentiation in LIRI, whereas miR-381 inhibition in BMSCs weakened these impacts. Mechanistically, miR-381 inhibited IL-18 translation in LMECs by inhibiting YTHDF1 expression via binding to its 3'-UTR. As expected, YTHDF1 overexpression in LMECs abolished the effects of miR-381-overexpressed exosomes on LMECs injury and Treg cell differentiation. Moreover, LMECs-secreted IL-18 inhibited Treg cell differentiation by promoting the ubiquitination degradation of Foxp3 protein. CONCLUSION: BMSCs-derived exosomal miR-381 suppressed IL-18 translation in LMECs through binding to YTHDF1 3'-UTR, thus suppressing the ubiquitination degradation of Foxp3 in CD4+ T cells, which promoted Treg cell differentiation and mitigated LIRI development.

The power of small: microRNAs modulating stomatal movement.

Regulation of stomatal aperture is paramount in drought-stress responses. Recently, Yang et al. demonstrated how microRNA-plantacyanin (PCY) regulates stomata movement by revealing a novel mechanism responsive to abscisic acid (ABA) that controls reactive oxygen species (ROS) in guard cells. This sets a precedent for using miRNAs as a new target for stress-resistance genetic engineering.

MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase-signal transducer and activator of transcription pathway.

Significant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties, exerts profound physiological effects on innate immunity by regulating interferon-stimulated genes (ISGs) within cells. However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. MiR-122-3p and miR-122-5p_R+1 were the most enriched miRNAs involved in the pathogenesis of IFN-α-induced inflammatory responses and were significantly downregulated by IFN-α treatment. Furthermore, we identified interferon induced protein with tetratricopeptide repeats 1 (IFIT1) as a potential target gene of miR-122. IFN-α markedly increased the expression of proinflammatory cytokines and fibrogenic genes but decreased the mRNA expression of ISGs. Additionally, IFN-α significantly activated the NF-κB p-p65, MAPK p-p38, and Jak/STAT pathways to trigger inflammation. Importantly, supplementation with a miR-122 mimic significantly alleviated IFN-α-induced inflammation and induced IFIT1 expression in LO2 cells. Conversely, the suppression of miR-122 markedly exacerbated the inflammatory response triggered by IFN-α. Furthermore, silencing IFIT1 via an siRNA elicited an inflammatory response, whereas IFIT1 overexpression ameliorated hepatic inflammation and fibrosis in a manner comparable to that induced by IFN-α treatment. Taken together, our findings suggest that miR-122 and its target, IFIT1, reciprocally regulate the inflammatory response associated with IFN through the Jak/STAT pathway.

Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA.

BACKGROUND: A spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study. OBJECTIVE: This study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI). METHODS: iPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining. RESULTS: The results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration. CONCLUSION: These results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.

Diagnostic value and clinical significance of serum miR-134-5p combined with uterine artery color Doppler ultrasound parameters in endometriosis.

OBJECTIVE: To exploit the combination diagnostic performance of serum microRNA-134-5p (miR-134-5p) and color Doppler ultrasound in patients with endometriosis patients. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) analysis was applied to measure relative abundance of miR-134-5p in serum of patients with endometriosis and gynecological benign diseases. Calculation of uterine artery blood flow parameters was conducted using Color Doppler ultrasound. Receiver operating characteristic (ROC) curve was established to evaluate the diagnostic capacity of miR-134-5p and Doppler parameters. Kaplan-Meier method was used for the analysis of recurrence-free survival rate. RESULTS: Compared with the control group, serum miR-134-5p expression was remarkably diminished in endometriosis patients (P < 0.001). End-diastolic velocity (EDV) and peak systolic velocity (PSV) were notably decreased in endometriosis patients compared with the control group (P < 0.001), while pulsatility index (PI) and resistance index (RI) were distinctly increased (P < 0.001). Serum miR-134-5p expression was positively correlated with EDV (r = 0.5777, P < 0.0001) and PSV (r = 0.6945, P < 0.0001), but negatively correlated with PI (r=-0.6382, P < 0.0001) and RI (r=-0.6247, P < 0.0001). The area under the ROC curve (AUC) of serum miR-134-5p combined with Doppler parameters was 0.905, with the sensitivity of 87.40%, and the specificity of 82.29%. The recurrence-free survival time was shorter in patients with low miR-134-5p expression than those with high miR-134-5p expression (P = 0.013). CONCLUSION: A better diagnostic value of endometriosis detection could be obtained when serum miR-134-5p was combined with Doppler parameters.

Extracellular vesicle-mediated delivery of miR-766-3p from bone marrow stromal cells as a therapeutic strategy against colorectal cancer.

OBJECTIVE: As colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths, understanding novel therapeutic mechanisms is crucial. This research focuses on the role of extracellular vesicles (EVs) from bone marrow stromal cells (BMSCs) in delivering miR-766-3p to CRC cells, targeting the MYC/CDK2 signaling axis. METHODS: Differentially expressed genes between BMSCs-EVs and CRC were identified using the Gene Expression Omnibus database. miR-766-3p target genes were predicted via TargetScan and RNAInter, with protein interactions analyzed using the STRING database. The analysis included RT-qPCR and Western blot on samples from 52 CRC patients. Characterization of BMSCs-EVs was followed by their functional assessment on CRC cell lines and the normal colon cell line CCD-18CO, evaluating cellular uptake, proliferation, migration, invasion, and apoptosis. RESULTS: miR-766-3p was confirmed in BMSCs-EVs and found underexpressed in CRC. BMSCs-EVs transported miR-766-3p to CRC cells, inhibiting their proliferation, migration, and invasion while promoting apoptosis. miR-766-3p targeted MYC, leading to decreased CDK2 transcription. Overexpression of MYC in HCT-116 cells counteracted these effects. In vivo studies showed that BMSCs-EVs carrying miR-766-3p hindered tumor growth. CONCLUSION: The study demonstrates the efficacy of BMSCs-EVs in delivering miR-766-3p to CRC cells, leading to the suppression of the MYC/CDK2 signaling pathway and hindering cancer progression.

Predictive value of miR-636 in patients with acute myocardial infarction undergoing percutaneous coronary intervention and its bioinformatics analysis.

BACKGROUND: MicroRNAs (miRNAs) play an important role in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI). Percutaneous coronary intervention (PCI) is currently the most direct and effective procedure to treat AMI, but the occurrence of postoperative cardiovascular events (MACE) affects patients' quality of life. The objective of this study was to identify a new biomarker that could provide a theoretical basis for the prevention of MACE in patients with AMI undergoing PCI. METHODS: 142 AMI patients who underwent PCI and 130 healthy volunteers were selected as study subjects. Detection of miR-636 expression level by fluorescence quantitative PCR. ROC, Kaplan-Meier and Cox regression analyses were applied to evaluate the diagnostic and prognostic value of miR-636 for AMI. The miR-636 target genes were predicted and enriched for GO function and KEGG pathway. RESULTS: MiR-636 expression levels were elevated in patients with AMI. ROC curve analysis showed that miR-636 had a feasible diagnostic value in distinguishing AMI patients from healthy controls miR-636 expression levels were elevated in patients who developed MACEs. ROC results showed that miR-636 had significant diagnostic value in differentiating AMI patients with and without MACEs after PCI treatment. GO and KEGG enrichment analyses showed that miR-636 may transmit information to vesicles formed by the cell membrane. CONCLUSIONS: MiR-636 expression serves as a biomarker for diagnosing AMI and predicting the occurrence of MACE after PCI.

Oxycodone alleviates LPS-induced neuroinflammation by regulating the CREB/miR-181c/PDCD4 axis.

BACKGROUND: Neuroinflammation plays a critical role in various neurological disorders. Oxycodone has anti-inflammatory properties. The purpose of this work was to look into the effect of oxycodone in controlling lipopolysaccharide (LPS)-induced neuroinflammation in microglia. METHODS: LPS-induced HMC3 cells were subjected to oxycodone (2.5, 5, 10 and 20 µg/mL). The mRNA and protein expressions were examined by qRT-PCR and western blotting. TNF-α, IL-1ß, IL-6, and IL-8 levels were assessed by ELISA. MTT assay was adopted to measure cell viability. The interactions between CREB, miR-181c and PDCD4 were analyzed by dual-luciferase reporter assay, ChIP and/or RIP assays. RESULTS: Oxycodone treatment alleviated LPS-induced inflammation in HMC3 cells and increased p-CREB level, but reduced PDCD4 and iNOS levels in LPS-treated cells. Mechanistically, oxycodone mitigated LPS-induced neuroinflammation by upregulating miR-181c. In addition, CREB promoted miR-181c expression by directly binding to the MIR181C promoter, and miR-181c inhibited PDCD4 expression by directly binding to PDCD4 3'UTR. As expected, oxycodone alleviated LPS-induced neuroinflammation by regulating the CREB/miR-181c/PDCD4 axis. CONCLUSION: Oxycodone attenuated LPS-induced neuroinflammation in microglia by regulating the CREB/miR-181c/PDCD4 axis. These findings proved that oxycodone is a potential drug for treating neuroinflammation and elucidate the mechanisms involved.

Circular RNA circEZH2 Promotes Lung Adenocarcinoma Progression by Regulating microRNA-495-3p/Tumor Protein D52 Axis and Activating Nuclear Factor-Kappa B Pathway.

Background: It has been increasingly recognized that circular RNAs (circRNAs) act as a pivotal factor in the onset and progression of human malignancies. Yet, the specific activities and mechanistic roles of these RNAs in the context of lung adenocarcinoma (LUAD) are not fully understood. Methods: Microarray analysis identified a novel LUAD-associated circular RNA, termed hsa_circ_0006357 (also referred to as circEZH2). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized for the analysis of circEZH2 expression in tissues and cell lines. The characteristics of circEZH2 were verified by RNase R treatment and fluorescence in situ hybridization (FISH) assays. The functions of circEZH2 were detected by Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays. The molecular mechanism of circEZH2 was clarified through bioinformatics analysis as well as RNA pulldown, dual-luciferase reporter, RT-qPCR, and immunoblotting assays. The role of circEZH2 in vivo was investigated using a xenograft model. Results: This investigation revealed that circEZH2 expression was elevated in LUAD cell lines and tumor samples. This elevation was associated with enhanced cell proliferation, migratory capacity, epithelial-mesenchymal transition (EMT), and invasion in vitro. Conversely, silencing of circEZH2 in vivo resulted in a notable decrease in LUAD tumorigenesis, whereas its overexpression led to the opposite effects. Mechanistically, circEZH2 appeared to act as a sponge for miR-495-3p, facilitating the upregulation of tumor protein D52 (TPD52) and triggering the nuclear factor kappa B (NF-κB) signaling pathway, thus contributing to the progression of LUAD. Conclusion: These findings indicate that circEZH2 may function as a competitive endogenous RNA (ceRNA), driving the progression of LUAD by manipulating the miR-495-3p/TPD52 axis and activating the NF-κB pathway.

Circ_0015382 Regulates the miR-942-5p/NDRG1 Axis to Suppress Trophoblast Cell Functions.

Circular RNAs (circRNAs) are non-coding RNAs that exert vital function in many human diseases, including preeclampsia (PE). Circ_0015382 is considered to be a key regulator of PE progression, so more molecular mechanisms need to be further studied. Real-time quantitative PCR was used to detect the mRNA levels of circ_0015382, miR-942-5p, and N-myc downstream regulated 1 (NDRG1). Western blot analysis was conducted to assess the protein levels. MTT and EdU assays were used to assess cell proliferation. Cell invasion was analyzed by transwell assay. Tube formation assay was conducted to detect cell angiogenesis. Dual-luciferase reporter assay and RNA immunoprecipitation were used to analyze the target relationship between miR-942-5p and circ_0015382 or NDRG1. Our data showed that circ_0015382 and NDRG1 were up-regulated, while miR-942-5p was down-regulated in the placental tissues of PE patients. Trophoblast cell proliferation, invasion, and angiogenesis were promoted by knockdown of circ_0015382. Circ_0015382 could sponge miR-942-5p, and NDRG1 was a target of miR-942-5p. MiR-942-5p inhibitor could reverse the promoting effects of si-circ_0015382 on trophoblast cell functions. Besides, the enhancing effects of miR-942-5p mimic on trophoblast cell proliferation, invasion, and angiogenesis could be eliminated by NDRG1 overexpression. In conclusion, our data showed that circ_0015382 inhibited trophoblast cell proliferation, invasion, and angiogenesis through regulating miR-942-5p/NDRG1 axis, providing a new mechanism for the regulation of PE progression.