Expression Of miR-21 Research Articles

MiR-211 regulates cutaneous wound healing through inhibiting inflammatory reactions and oxidative stress by binding SOX11.

Loss of skin integrity due to a wound or disease can lead to severe disability or even life threat. The highly expressed microRNAs in the skin are of great significance for skin development. The investigation purposed to explore the effect and mechanism of miR-211 on inflammation, oxidative stress and migration in keratinocytes. The HaCaT keratinocytes were treated with hydrogen peroxide (H2O2) to establish a wound-healing model. The expression of miR-211 was examined by quantitative real-time PCR (qRT-PCR). The cell function was reflected in proliferative ability, migration, apoptosis, and inflammation, which were evaluated by Cell Counting Kit-8 (CCK-8) assay, Transwell test, flow cytometry technique, and enzyme-linked immunosorbent assay (ELISA). The target of miR-211 was verified by luciferase luminescence measurements. H2O2 inhibited HaCaT cell proliferation, migration, and promoted cell apoptosis, accompanied with the downregulation of miR-211. H2O2 led to inflammatory response and oxidative damage to HaCaT. MiR-211 promoted proliferation and migration, but improved cell apoptosis of HaCaT. The role of H2O2 on inflammatory response and oxidative stress was alleviated by miR-211. SRY-box transcription factor 11 (SOX11) was a targeted mediator of miR-211. SOX11 reversed the influence of miR-211 on cell proliferation, migration, apoptosis, inflammatory response and oxidative stress. MiR-211 regulated proliferation, migration, apoptosis, inflammation and oxidative stress of keratinocytes by mediating SOX11, thus participating in cutaneous wound healing.

The correlation between miR-21 single nucleotide polymorphisms and the susceptibility of non-small cell lung cancer

BackgroundThere are still gaps in the study of the miRNA and its SNPs in some diseases such as non-small cell lung cancer (NSCLC). The study aimed to provide useful information on the treatment of NSCLC by investigating the association between miR-21 and its SNPs and NSCLC susceptibility.MethodsThe serum of NSCLC patients (n = 205) and cancer-free controls (n = 217) were collected in this study for RNA extraction. The qRT-PCR was used to evaluate the expression of miR-21 and Taqman qPCR was used for genotyping and quantifying miR-21 SNPs (rs1292037, rs6504593). The association of the expression of miR-21, the miR-21 SNPs and their interactions with the susceptibility of NSCLC patients were analysed using logistic regression analysis in this study.ResultsThis study showed that the overexpression of miR-21 was related to NSCLC. The C allele and CC genotypes of rs1292037 and rs6504593 were associated with the increased risk of NSCLC susceptibility. Moreover, the interactions of rs1292037 and rs6504593 were also a risk factor for NSCLC. The CC genotypes of rs1292037 and rs6504593 were associated with the increase of miR-21 expression.ConclusionThe overexpression of miR-21, the miR-21 SNPs rs1292037 and rs6504593 and their interactions were associated with NSCLC susceptibility. MiR-21 and its SNPs have potential for being targets in the therapy of NSCLC. This study provided important information for the treatment of NSCLC.

Microglia-derived exosomal ciRS-7 mediates IL-17A effect of promoting neurodegeneration via miR-7 and SNCA targets in an experimental Parkinson's disease.

Parkinson' s disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra (SN). Our research has demonstrated that the levels of interleukin (IL)-17A are elevated in the SN of rodent models of PD, and that IL-17A accelerates neurodegeneration in PD depending on microglial activation. Furthermore, existing studies indicate that exosomes released by activated microglia may play a significant role as mediators of neurodegeneration in PD. Herein, we demonstrated that BV-2-derived exosomes were taken up by ventral mesencephalic (VM) dopaminergic neurons, and mediated IL-17A effect of promoting dopaminergic neuronal injury. IL-17A-treated BV-2-derived exosomes altered neuronal miR-7 and SNCA expression and promoted dopaminergic neuronal injury in vitro. Inhibiting BV-2 exosome formation and secretion by GW4869 alleviated dopaminergic neuronal injury. Silencing ciRS-7 in BV-2 altered neuronal miR-7 and SNCA expression and mitigated dopaminergic neuronal injury. Overexpression of ciRS-7 in VM neurons altered neuronal miR-7 and SNCA expression and promoted dopaminergic neuronal injury. Injection with exosomes derived from IL-17A-treated BV-2 altered ciRS-7, miR-7 and SNCA expression in SN in MPTP-intoxicated mice and promoted nigrostriatal dopaminergic neurodegeneration and motor impairment. However, injection with exosomes derived from IL-17A and ciRS-7-shRNA treated BV-2 attenuates the manifestations mentioned above. These findings suggest that microglia-derived exosomal ciRS-7 mediates IL-17A effect of promoting neurodegeneration via miR-7 and SNCA targets and may provide a new paradigm to study the pathology of PD.

Expression and characterization of exosomal miRNAs in healthy, sub-clinical mastitis and pasteurized milk of buffaloes

Our research on the expression and characterization of exosomal miRNAs in buffalo milk, particularly in the context of healthy, sub-clinical mastitis and pasteurized milk, is a novel contribution to the field. We are the first to investigate the expressions of miRNAs and the characterization of exosomes in boiled and pasteurized milk. This study is based on clinical signs and CMT, where twenty buffalo milk samples were divided into normal and sub-clinical mastitis and a third group of ten commercial pasteurized milk. The SCC differed significantly (p < 0.001) in all the groups before boiling. The data analysis demonstrated elevated differential expression of miR-148a and miR-186 in sub-clinical mastitis and pasteurized milk compared to normal milk before and after boiling. The positive correlation between SCC and miR-148a and miR-186 expression indicates their potential as robust biomarkers for sub-clinical mastitis in buffaloes. The miR-148a and miR-186, known to play roles in various diseases like cancer, can withstand commercial pasteurization and boiling, raising the intriguing possibility of transferring through milk exosomes. This finding underscores the need for clean milk production and the importance of understanding the mechanisms of miRNA transfer between species, which is crucial for the future of animal health and milk production.

Identification and validation of an immune-related miRNA signature for predicting prognosis of hepatocellular carcinoma.

MicroRNAs play a significant role in the initiation and progression of hepatocellular carcinoma (HCC); however, their roles in immune regulation of HCC remain unclear. Our study aimed to identify an immune-related miRNA signature and explore its impact on the prognosis and tumor immune microenvironment HCC. Initially, we identified 48 differentially expressed immune-related miRNAs. Using the LASSO regression dimensionality reduction method, we constructed an immune-related miRNA signature from 12 of these miRNAs. This signature has emerged as an independent prognostic marker and is associated with the clinical stage of HCC. To elucidate the roles of the twelve-microRNA signature, we predicted their target genes. Enrichment analysis indicated that these target genes were involved in immune cell infiltration. Notably, the target genes regulated by hsa-miR-139-5p, hsa-miR-551a, and hsa-miR-7-5p showed a partial overlap. We further confirmed the differential expression of miR-7, miR-551a, miR-139-5p, and some of their overlapping target genes in tumor and non-tumor tissues derived from patients with HCC using RT-qPCR. Overall, we identified an immune-related miRNA signature that is strongly correlated with the prognosis and immune microenvironment of HCC; and confirmed the differential expression of the three most important microRNAs and their overlapping target genes in tumor and non-tumor tissues derived from HCC patients.

Circulating miR-29c, miR-195, and miR-486 Are Objective Indicators to Determine the Moderate Intensity of Resistance Exercise.

Background and objective Moderate exercise is important for health; however, there are variations among individuals in terms of characterizing moderate intensity and it is difficult to identify. In light of this, the purpose of this study was to identify new objective indicators to determine effective exercise intensity. Methods This study involved both human and animal experiments. After subjectingmice to exercise of effective intensity, microarray analysis of circulating microRNA expression was conducted to identifycandidates for objective indicators to determine effective exercise intensity. Then, we assessed if these microRNAs were altered after aerobic or resistance exercises in humans using quantitative real-time PCR. Twelve healthy males were randomly assigned to two groups: the low-intensity exercise group (LI group) and the high-intensity exercise group (HI group) and they underwent four weeks of exercise program. Results Based on microarray analysis, 188 microRNAs were altered after aerobic exercise, and 167 microRNAswere altered after resistance exercise. Combining these findings with the data from some published reports, we selected miR-29c, miR-23b, miR-222, miR-195, miR-126, miR-133a, and miR-486 as the candidates for biomarkers to determine the effective exercise intensity. In the human study, physical performance improved after resistance exercise only in the HI group. Of themicroRNAs, miR-29c, miR-195, and miR-486 increased immediately after resistance exercise only in the HI group. Fold change of miR-486 correlated with changes in knee extensor strength (r=0.744, p=0.005). Conclusions Resistance exercise ateffective intensity upregulated the expression of miR-29c, miR-195, and miR-486. Hence, these microRNAs may serve as objective indicators to determine the intensity of resistance exercise. Among them, miR-486 may aid in predicting the response to resistance exercise.

CRNDE alleviates IL-1β-induced chondrocyte damage by modulating miR-31/NF-κB pathway

BackgroundThe long non-coding RNA CRNDE (CRNDE) has been identified as a lncRNA associated with osteoarthritis (OA), playing a role the age-related degeneration of articular cartilage. However, the precise mechanism by which CRNDE affects the physiological functions of OA chondrocytes remains unclear.MethodsTo simulate the inflammatory conditions observed in OA, interleukin (IL)-1β-stimulated chondrocyte C-28/I2 cells were utilized. The expression levels of CRNDE and miR-31 were assessed using reverse transcription-polymerase chain reaction (RT-PCR). Chondrocyte viability and apoptosis were evaluated through CCK-8 assay and flow cytometry, respectively. The levels of IL-6, IL-1β and Tumor necrosis factor (TNF-α) were determined using enzyme-linked immunosorbent assay (ELISA). mRNA expression levels of MMP-13, Aggrecan and COL2A1 were detected by quantitative RT-PCR. Western blot analysis was performed to evaluate the protein levels of factors related to cartilage matrix degradation, including p-p65, p65 and p-IκBα of the NF-κB pathway.ResultsCRNDE expression was downregulated in both OA cartilage tissues and IL-1β-stimulated chondrocytes. Overexpression of CRNDE mitigated IL-1β-stimulated chondrocytes apoptosis, inflammatory responses, and cartilage matrix degradation. Compared with healthy controls, OA tissues exhibited reduced expression of miR-31, which was negatively correlated with the expression of CRNDE. Additionally, overexpression of miR-31 partially reversed the inhibitory effects of CRNDE on apoptosis, inflammation, cartilage matrix degradation, and the inactivation of Nuclear factor (NF)-κB pathway induced by IL-1β stimulation. Moreover, silencing of CRNDE exacerbated IL-1β-induced chondrocytes damage, which was aliviated by the NF-κB pathway inhibitor, Bay 11-7082.ConclusionCRNDE alleviated IL-1β-induced injuries in OA chondrocytes by suppressing the miR-31-mediated NF-κB signaling pathway.

NF-κB/Relish readjusts miR-100 expression and recovers immune homeostasis in Drosophila melanogaster.

The regulation and maintenance of immune homeostasis are essential for animal survival, but the molecular mechanisms are not fully understood. Here, we used the model organism Drosophila melanogaster to uncover a potential mechanism by which the nuclear factor-κB transcription factor Relish and miR-100 cooperatively regulate innate immune homeostasis. We first demonstrated in vitro and in vivo that miR-100 can negatively regulate the immune responses of the Imd pathway by inhibiting the expression of TAK1-associated binding protein 2 (Tab2) gene. Second, we found that Relish, an important transcription factor in the Drosophila Imd pathway, could not only modulate the expressions of antimicrobial peptides (AMPs) to promote immune responses, but also bind to the promoter region of miR-100 and activate its transcription to inhibit immune responses. Third, the dynamic expression of genes profiling indicated that the Relish/miR-100/Tab2 regulatory axis could contribute to innate immune homeostasis in Drosophila. Together, our findings reveal the dual role of Relish in immune regulation, that is, Relish promotes the expression of AMPs to resist pathogen infection in the early immune response, while in the late immune stages, Relish readjusts the expression of miR-100 to negatively control immune responses to avoid excessive immunity thus maintaining immunohomeostasis. Meanwhile, our study provides a new perspective for further understanding the complex regulatory mechanism of immune homeostasis in animals.

Loc646329 sponges miR-21 to reduce RAS/MAP kinase signaling pathway in oral squamous cell carcinoma (OSCC).

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of head and neck cancer. Emerging evidence suggests that microRNAs (miRNAs) play a crucial role in the development and progression of OSCC. In particular, miR-21 has been implicated in various cellular processes, including proliferation, apoptosis, and invasion; it could be a potential therapeutic target for OSCC. In this study, The Cancer Genome Atlas (TCGA) for OSCC (TCGA-OSCC) clinical information was used. Patient outcomes were analyzed through survival analysis using Kaplan-Meier curves and log-rank tests. The HSC-3cell line was used as the OSCC cell line, which is known for its aggressive characteristics. The expression of Loc646329, miR-21, PTEN, PDCD4, and SPRY2 was evaluated by RT-PCR, flow cytometry, and scratch assay. Also, the effect of Loc646329 expression on OSCC was evaluated using the in vivo Xenograft Mouse Model. The results showed that overexpression of Loc646329 leads to the downregulation of miR-21, PDCD4, and SPRY2 genes while the PTEN gene is upregulated. In other words, the overexpression of Loc646329 by miR-21 inhibition (thorough targeting RAS/MAPK pathway) induces apoptosis and stops the cell cycle in OSCC cells. In vivo tests showed that elevated Loc646329 expression was linked to positive pathological outcomes, such as smaller tumor size, reduced lymph node metastasis, and enhanced overall survival in OSCC patients. In conclusion, the identification of Loc646329 as a sponge for miR-21 and its impact on the RAS/MAPK signaling pathway offers new opportunities for the development of innovative therapeutic strategies for OSCC. Further investigations into this regulatory axis may uncover additional targets for precision medicine approaches in the treatment of OSCC.

Effects of miR-21/NLRP3 on Blue Light-Induced Retinal Neurodegeneration in Mice

Purpose Age-related macular degeneration (AMD) is a chronic retinal disease that can lead to blindness. While the NLR family pyrin domain containing 3 (NLRP3) inflammasome is implicated in AMD, the specific roles of miR-21 and NLRP3 in AMD-related inflammation remain unclear. Therefore, this study aimed to investigate the roles of miR-21 and NLRP3 in blue light-induced neurodegeneration in the mouse retina. Methods A mouse model of retinal light damage was established through three months of blue light exposure (BLE). The experimental groups comprised the Control (Ctrl), BLE, BLE + miR-nc, and BLE + miR-21 inhibitor groups. The microRNAs were administered via intravitreal injections once per week. After successful modeling, changes in visual function and retinal morphology were investigated by using electroretinography and hematoxylin and eosin staining, respectively. Photoreceptor apoptosis was assessed using the TdT-mediated dUTP nick-end labeling assay. Immunofluorescence was used to detect and locate microglia and NLRP3 expression in the mouse retina. The expression of miR-21, NLRP3, and downstream factors in the retinas of each group was measured using qRT-PCR and western blotting. Results In the BLE and BLE + miR-nc groups, there was a decrease in visual function and retinal thickness, an increase in retinal ganglion cell injury and photoreceptor cell apoptosis, and elevated microglia activity in the retina, as evidenced by their migration to the outer retinal layer. In addition, the expression of miR-21, NLRP3, and downstream factors was increased in the BLE and BLE + miR-nc groups compared to that in the control group. However, intravitreal injection of the miR-21 inhibitor reduced miR-21 expression in the retina and significantly inhibited the activation of the NLRP3 inflammasome, effectively alleviating retinal photodamage caused by BLE. Conclusions This study indicates that miR-21 may mitigate blue-light-induced retinal neurodegeneration by reducing the activation of the NLRP3 inflammasome in the mouse retina.

Dysregulation of MiR-21, MiR-221 and MiR-451 During Neoadjuvant Treatment of Breast Cancer: A Prospective Study.

Breast cancer is highly heterogeneous disease in which different responses are observed to the same treatment for different subtypes and extents of similar diseases. Considering this scenario, the search for tumor biomarkers is indispensable, with current evidence suggesting that circulating microRNAs are viable biomarkers. This study evaluated the expression of miR-21, miR-221, miR-195, and miR-451 in patients with breast cancer undergoing neoadjuvant treatment at oncology outpatient facilities in Brazil. We conducted a prospective and observational study in which blood samples were collected for microRNA expression analysis, comparing control and breast cancer patients who were candidates for neoadjuvant treatment groups. The expression of microRNAs was investigated by qRT-PCR method. For parametric data analysis, one-way ANOVA with Tukey's post hoc test was used. Thirty-three participants (all female) were included in the control group and twenty-seven participants were included in the study group. The non-special subtype of breast cancer was found in 96% of the study group participants; 88.9% were locally advanced tumors (T3, T4), 40.7% were luminal tumors, 33.3% were HER-2-positive, and 26% were triple negative tumors. Expression analysis of microRNAs during neoadjuvant treatment, using miR-16 as a normalizer, showed higher expression levels of miR-21 and miR-221 at the end of treatment, and high expression levels for miR-451 were also observed at the beginning of treatment. This is the first study that evaluates the expression of microRNAs in the context of neoadjuvant treatment of breast cancer in the Brazilian population. Our results suggest that there is a deregulation of miR-21, miR-221, and miR-451 during neoadjuvant treatment in these patients.

MiRNA-34a, miRNA-145, and miRNA-222 Expression, Matrix Metalloproteinases, TNF-α and VEGF in Patients with Different Phenotypes of Coronary Artery Disease.

The development of different phenotypes of coronary artery (CA) lesions is regulated via many various factors, such as pro-inflammatory agents, zinc-dependent endopeptidases, growth factors and circulating microRNAs (miRs). To evaluate the expression levels of miR-34a, miR-145 and miR-222, tumor necrosis factor α (TNF-α), matrix metalloproteinases (MMP-1, -9, -13 and -14) and vascular endothelial growth factor (VEGF) in patients with different phenotypes of coronary artery disease (CAD): ischemia/angina with non-obstructive coronary arteries (INOCA/ANOCA) and obstructive CAD (oCAD) compared with a control group. This cross-sectional observational study included 157 subjects with a verified CAD diagnosis (51 patients with INOCA, 76 patients with oCAD and 30 healthy volunteers). The expression of miR-34a, miR-145 and miR-222 (RT-PCR) and the levels of VEGF, TNF-α, MMP-1, MMP-9, MMP-13 and MMP-14 (ELISA) were estimated in plasma samples. A higher concentration of MMP-9 was found in oCAD-group samples compared to the INOCA/ANOCA group. The INOCA/ANOCA group was characterized by higher levels of TNF-α. Based on multivariate regression analysis, a mathematical model predicting the type of CA lesion was constructed. MiR-145 was the independent predictor of INOCA/ANOCA (p = 0.006). Changes in concentrations of MMP-9 and MMP-14 were found in both investigated CAD groups, with MMP-9 levels being significantly higher in obstructive CAD samples than in INOCA/ANOCA, which confirms the role of inflammation in the development of atherosclerosis. A multivariate regression analysis allowed us to achieve a model that can predict the phenotype of stable CAD, and MiR-145 can be assumed as an independent predictor of INOCA/ANOCA.

Therapeutic Potential of Alpha-pinene in Breast Cancer: Targeting miR-21 and PTEN Gene Expression

Background: Alpha-pinene is an organic compound with anticancer properties. This compound has been used as a therapeutic factor in breast cancer (BC). miR-21 causes cancer cell invasion by inhibiting Phosphatase and tensin homolog (PTEN). The present study evaluates the potential effect of Alpha-piene on the expression of PTEN and miR-21 genes in BC cells (MCF-7 cell line). Materials and Methods: In this study, the MCF-7 cell line was used. The cells were treated with Alpha- pinene. The viability of cells with different Alpha-pinene concentrations (i.e., 40, 50, 100, 150, and 200 μM) was evaluated with MTT assay. The expression of PTEN and miR-21 genes was evaluated using RT-qPCR. Results: The survival rate of cells in all concentrations was higher 24 h after treatment compared to 48 h after the treatment (P&lt;0.0001). The expression of miR-21 in cells treated with 100 and 50 μM of Alpha- pinene reduced significantly compared to the control cells(P&lt;0.001). PTEN gene expression was exactly the opposite of miR-21. Therefore, its expression increased significantly in cells treated with 100 μM of Alpha- pinene compared to the control cells (P&lt;0.0001). Conclusion: In general, the use of Alpha- pinene led to decreased and increased expression of miR-21 and PTEN, respectively. These changes lead to the reduction of invasion and proliferation of BC cells. Therefore, the Alpha- pinene combination can be used as a therapeutic strategy to treat patients.

MicroRNA-21 expression as a novel diagnostic and prognostic biomarker in oral cancer: A narrative review

Background: Oral cancer is a life-threatening disease that has 377.713 new cases every year and 60% of the 5-year overall survival rate globally. Approximately 84–97% of oral cancer arises from squamous cells, categorized as oral squamous cell carcinoma (OSCC). MiR-21 is a single-stranded, non-coding RNA that has been studied for its role in carcinogenesis. Overexpression of miR-21 is found in various cancers and is linked to a poor prognosis. However, few studies analyze the expression of miR-21 as a diagnostic and prognostic biomarker in oral cancer. Purpose: This review aimed to describe the expression of miR-21 as a novel diagnostic and prognostic biomarker in oral cancer. Review: MiR-21 was found to be upregulated in various cancers, including oral cancer. miR-21 targets several tumor suppressors such as PTEM, TPM1, and PDCD4 to modulate characteristics linked to cancer prognosis, including cell proliferation, apoptosis, invasion, and metastasis. Furthermore, the constant increase of miR-21 expression in healthy oral mucosa to oral potentially malignant disease to OSCC demonstrated its diagnostic value. Conclusion: miRNA-21 may act as a novel diagnostic and prognosticbiomarker of oral cancer.

Effects of electroacupuncture on expression of miR-218 and HMGB1/TLR4 signaling pathway in rats with focal cerebral ischemia

To observe the effect of electroacupuncture (EA) on high mobility group box 1 (HMGB1) / toll-like receptor 4 (TLR4) signaling pathway and inflammatory injury in rats with focal cerebral ischemia (FCI), so as to explore its mechanisms underlying amelioration of ischemic stroke. Male SD rats were randomly divided into sham operation (n=18), model (n=18) and EA (n=18) groups. The FCI model was established according to Longa's method. In the EA group, 24 h after modeling, EA stimulation was applied to "Baihui"(GV20), "Fengfu"(GV16), and "Neiguan" (PC6) and "Xinshu" (BL15) on the left side for 20 min, once a day for 1 week. The neurological deficit severity was evaluated by the modified neurological severity score (mNSS), and the morphological changes of neurons were observed after H.E. staining. The expression of HMGB1 and TLR4 proteins were detected by immunofluorescence staining. The contents of tumor necrosis factor(TNF)-α and interleukin(IL)-6 in the ischemic area tissue of the brain were detected using ELISA. The mRNA expressions of HMGB1 and TLR4 as well as the expression of miR-218 in the ischemic cortex were detected by PCR. Compared with the sham operation group, the mNSS at 2 h, 48 h and 7 day (d), IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 48 h and 7 d were significantly increased (P<0.01), while miR-218 expression at 48 h and 7 d was obviously down-regulated (P<0.01) in the model group. In comparison with the model group, the mNSS at 7 d, IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 7 d not at 48 h were significantly decreased (P<0.01, P<0.05), while the expression of miR-218 at 7 d was apparently up-regulated (P<0.05) in the EA group. H.E. staining showed that there were signs of neuronal necrosis including blurred outline of the cells, disordered internal structure, dense cytoplasm, shrunk nuclei, etc. in the ischemic area of the brain at 48 h and 7 d in the model group, which was evidently milder on day 7 in the EA group. EA can reduce the inflammatory injury of brain tissue and improve the neurological impairment in rats with FCI, which may be associated with its effects in inhibiting HMGB1/TLR4 signaling and down-regulating the level of pro-inflammatory cytokines.

The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population

Bone tissue is constantly regenerated and repaired through a finely balanced process known as bone remodeling. Many miRNAs act as regulators of the signaling pathways involved in bone metabolic processes to maintain tissue homeostasis. This study aimed to assess the circulating levels of MIR21, MIR34a, and MIR155 in human serum and their bone expression, and the expression of bone turnover-related genes which can reflect the bone quality. This prospective study was conducted on 60 patients (30 males and 30 females) indicated for surgical interventions for neural decompression +/- fixation. Relative quantification of expression of MIR21, miR34a, and MIR155 and bone related genes was assayed using PCR. The serum levels of osteocalcin and Serum Bone Alkaline Phosphatase (sBAP) were assayed using a human ELISA kit. The main finding of the present work was the strong positive association between the circulating levels of only miR21 and MIR155 and their bone expression in the population under study and with bone markers and target genes Also, a positive association was found between both bone expression and circulating MIR21 levels with age and sBAP. These results suggest that the circulating levels of these microRNAs as early markers for the predication of bone quality.

Expression of Salivary miRNAs, Clinical, and Demographic Features in the Early Detection of Gastric Cancer: A Statistical and Machine Learning Analysis.

Gastric cancer ranks as one of the top five deadliest cancers worldwide and is often diagnosed at late stages. Analysis of saliva may provide a non-invasive approach for detection of malignancies in organs associated with the oral cavity. This research aims to analyze salivary microRNA expression together with clinical and demographic features with the aim of diagnosing gastric cancer. The study included 19 patients with early-stage gastric cancer and 19 healthy controls. Saliva samples were collected and processed for RNA isolation. Salivary expression of miR-223-3p and miR-21-5p were measured using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were generated to evaluate the accuracy of diagnostic models. Machine learning algorithms, multiple logistic regression, and principal component analysis (PCA) were used to assess the predictive power of miRNAs in conjunction with clinical-demographic features. Significant upregulation of miR-223-3p and downregulation of miR-21-5p in saliva were observed in patients with gastric cancer. The area under ROC curve (AUC) values for salivary miR-21-5p, salivary miR-223-3p, and their multiple logistic regression were determined to be 0.723, 0.791, and 0.850, respectively. The AUC for multiple logistic regression model was 0.919. The PCA model led to the highest diagnostic odds ratio (DOR) of 134.33 (sensitivity = 0.785, specificity = 1.00, AUC = 903). Application of machine learning methods, and in particular a random forest algorithm, showed high accuracy in diagnosing patients with gastric cancer (sensitivity = 1.00, specificity = 0.857, AUC = 0.93). The application of validated salivary diagnostics in clinical practice could help facilitate earlier diagnosis of gastric cancer and improve medical outcome. Expression of miR-21 and miR-223-3p in saliva together with clinical and demographic features, appears promising in screening for GC.

MicroRNAs as Biomarkers for Metabolic Disorders in Polycystic Ovary Syndrome (PCOS): A Review.

Polycystic ovary syndrome (PCOS) is associated with several mild metabolic disorders, including insulin resistance (IR), obesity, and dyslipidemia, as well as with some more severe ones, including type 2 diabetes mellitus, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. Clinically, mild metabolic complications of PCOS such as IR or lipid metabolism disorders are the predictors of these more severe ones. So far, there is no reliable single marker that enables defining metabolic risk in patients with PCOS. Therefore, novel independent markers of metabolic disturbances are needed. Most reports have focused on microRNA (miRNA, miR) assessment in blood serum or granulosa cells, suggesting the high potential clinical utility of such management. The greatest number of studies focused on the association between miRNAs and IR, obesity, or lipid disorders, and some miRNAs were characteristics of all these processes concomitantly. The altered expression of miR-222, miR-223, miR-320, and miR-122 has been most commonly mentioned as the regulator of these metabolic distortions and seems to result from common regulation pathways of metabolic disturbances. In turn, the current literature lacked the miRNA which could be identified as a reliable marker of type 2 diabetes mellitus or NAFLD accompanying PCOS. Therefore, the main objective of future studies should be determining miRNA markers of these most serious metabolic complications. This article aims to review the role of microRNAs as biomarkers for metabolic disorders in PCOS.

The implication of TET1, miR-200, and miR-494 expression with tumor formation in colorectal cancer: through targeting Wnt signaling

ObjectiveColorectal cancer (CRC) is a diverse and multifaceted disease characterized by genetic and epigenetic changes that contribute to tumor initiation and progression. CRC pathophysiology has been linked to the deregulation of the Wnt signaling pathway and the ten-eleven translocation (TET) DNA demethylases. This study aimed to evaluate the expression level of selective miRNAs (miR-200 and miR-494), TET1, and Wnt1 in colorectal polyps, actual colorectal tumors, and normal adjacent tissues. We also evaluated the effect of 5-aza cytidine on the expression level of TET1 and wnt1 in the HT29 cell line.Materials and methodsIn this study, we assessed TET1 and Wnt1 expression in 5-azacytidine-treated HT29 cells, a demethylating agent commonly used in cancer therapy. Additionally, we enrolled 114 individuals who underwent radical surgical colon resection, including 47 with cancerous tissues and 67 with polyps. We utilized qRT-PCR to measure miR-200, miR-494, TET1, and Wnt1 mRNA levels in colorectal polyps, actual colorectal tumors, and normal adjacent tissues.ResultsOur study revealed that TET1 expression was notably lower in both polyps and CRC tissue compared to adjacent normal tissue, with higher TET1 expression in tumors than polyps. We also observed significant differences in miR-200 and miR-494 expression in tumor samples compared to adjacent normal tissue. Our in vitro experiments revealed that 5-azacytidine administration increased TET1 and decreased Wnt1 expression in CRC cell lines. This suggests that DNA-demethylating drugs may have a therapeutic role in modifying TET1 and Wnt signaling in the development of CRC.ConclusionsOverall, our findings shed light on the intricate interactions between TET1, Wnt1, and specific miRNAs in colorectal cancer (CRC) and their potential implications for diagnosis and treatment.

CDR1as Deficiency Prevents Photoreceptor Degeneration by Regulating miR-7a-5p/α-syn/Parthanatos Pathway in Retinal Detachment

Retinal detachment (RD) is the separation of the neural retina from the retinal pigment epithelium, with photoreceptor degeneration being a major cause of irreversible vision loss. Ischemia and hypoxia after RD decreased the level of miR-7a-5p (miR-7) and promoted the expression of its main target, α-synuclein (α-syn), which activated the parthanatos pathway and led to photoreceptor damage. Circular RNA CDR1as, which is an antisense transcript of cerebellar degeneration-related protein 1, functions as a "sponge" for miR-7, thereby regulating its abundance and activity. In this study, we first reported that CDR1as expression is elevated after RD. Adeno-associated virus serotype 9 vector containing the shRNA-CDR1as sequence was used to inhibit CDR1as expression via subretinal injection. Hematoxylin and eosin staining and transmission electron microscopy revealed that the morphology and outer nuclear layer thickness of the retina were preserved and photoreceptor cell death was decreased after experimental RD in mice. Mechanistically, CDR1as deficiency significantly increased the expression of miR-7, then decreased the expression of α-syn, poly (ADP-ribose) polymerase 1, apoptosis-inducing factor, and migration inhibitory factor. Furthermore, visual function was improved as shown by Morris water maze experiments in the mouse model of RD. Our findings suggest a surprisingly neuroprotective role for CDR1as deficiency, which is probably mediated by enhancing miR-7 activity and inhibiting α-syn/poly (ADP-ribose) polymerase 1/apoptosis-inducing factor pathway, thereby preventing photoreceptor degeneration.