miR-155 Levels Research Articles

Divergent roles of circulating miR-133 and miR-155 in modulating angiotensin II levels among hypertensive patients in Melanesian and non-Melanesian populations

The therapeutic approach to hypertension often varies across racial and ethnic groups; however, antihypertensive treatments have not yet been tailored to account for these variations in Indonesia, a country with diverse racial and ethnic groups. In addition, microRNA-133 (miR-133) and microRNA-155 (miR-155) play critical roles in cardiac muscle homeostasis and inflammatory responses, but their specific functions in hypertension remain unclear. The aim of this study was to investigate the correlation between circulating miR-133 and miR-155 levels and angiotensin II (ANG-II) levels in hypertensive patients from Melanesian and non-Melanesian populations in Indonesia. A cross-sectional study was conducted in Jayapura, Indonesia among Melanesian and non-Melanesian hypertensive patients. The levels of ANG-II were quantified using sandwich ELISA, while the relative expression of miR-133 and miR-155 levels were measured by real-time PCR. Differences between the two groups were assessed using the Mann-Whitney test, and correlations between miR and ANG-II levels were determined using the Spearman correlation test. The relative expression levels of miR-133 and miR-155 in the Melanesian group were significantly higher than in the non-Melanesian group; 6.94-fold (3.85 vs 0.55) and 2.1-fold higher (0.19 vs 0.09), respectively. MiR-133 had a moderate negative correlation with ANG-II in both Melanesian (r=-0.538; p<0.001) and non-Melanesian (r=-0.649; p<0.001). However, miR-155 had no significant correlation with ANG-II levels in either the Melanesian group (p=0.551) or non-Melanesian group (p=0.159). This study highlights that miR-133 levels are significantly correlated with ANG-II concentrations in both Melanesian and non-Melanesian hypertensive patients, suggesting that miR-133 may play a regulatory role in the ANG-II pathway. These findings provide insights into the potential of miR-133 as a biomarker for hypertension management in diverse populations.

MIR-155 as a potential biomarker for disease severity in st-segment elevation myocardial infarction: insights from a university-affiliated cardiovascular center.

MiR-155 plays a role in inflammatory pathways and cardiovascular diseases, though its relationship with inflammation, atherosclerosis, and outcomes in ST-elevation myocardial infarction (STEMI) is not well established. To investigate associations between miR-155 levels, inflammation, atherosclerotic burden, and major adverse cardiovascular events (MACE) in STEMI patients. Sixty-nine STEMI patients and 16 healthy controls were recruited from a specialized university-affiliated cardiovascular center. MiR-155 expression and serum interleukin (IL)-1β, IL-6, and tumor necrosis factor levels were measured. Patients were grouped into tertiles based on miR-155 expression. Clinical data, atherosclerotic burden (through cardiac catheterization), and in-hospital MACE were recorded. MiR-155 levels were significantly lower in STEMI patients compared to controls (median 54.2, vs. 152.8 arbitrary units; p = 0.003). Higher miR-155 tertiles were associated with a greater prevalence of three-vessel occlusion (34% vs. 13% vs. 4%; p = 0.007) and increased incidence of pulmonary edema (13% vs. 0% vs. 0%; p = 0.030). No significant correlation was found between miR-155 and inflammatory or myocardial markers. Dysregulated miR-155 expression in STEMI patients may influence disease severity and MACE risk, independent of inflammation or myocardial damage markers.

Expression of some circulating microRNAs as predictive biomarkers for prognosis and treatment response in glioblastoma

Glioblastoma multiforme (GBM) is the most prevalent, treatment-resistant, and fatal form of brain malignancy. It is characterized by genetic heterogeneity, and an infiltrative nature, and GBM treatment is highly challenging. Despite multimodal therapies, clinicians lack efficient prognostic and predictive markers. Therefore, new insights into GBM management are urgently needed to increase the chance of therapeutic success. Circulating miRNAs (miRs) are important regulators of cancer progression and are potentially useful for GBM diagnosis and treatment. This study investigated how miR-29a, miR-106a, and miR-200a affect the prognosis of GBM patients. This study was conducted on 25 GBM patients and 20 healthy volunteers as a control group. The expression levels of target miRs were analyzed pre- and post-treatment using qRT-PCR and evaluated in relation to both clinical GBM criteria and the patient’s survival modes. The diagnostic efficacy of target miRs was assessed using the receiver operating characteristic (ROC) curve. MiRs levels showed significant differences among the enrolled participants. All investigated miRs were significantly elevated in GBM patients with non-frontal lesions. Only miR-200a showed a significant difference in GBM patients older than 60 years with a tumor size ≥ 5 mm. Regarding miR-106a, a significant difference was detected based on the surgical strategy and use of an Eastern Cooperative Oncology Group (ECOG) performance status equal to 2. For miR-29a, a significant upregulation was detected according to the surgical strategy. All post-treatment miRs levels in GBM patients were significantly downregulated. In conclusion, circulating miRs revealed a significant role in predicting GBM patient treatment outcomes providing valuable insights for personalized therapeutic strategies.

Muscle-specific miRNAs in plasma and skeletal muscle of patients with idiopathic inflammatory myopathy are modulated by disease and training.

Objective of this work was to examine myomiR levels in plasma, skeletal muscle, and skeletal muscle cells of patients with idiopathic inflammatory myopathy (IIM), their interrelations with the disease-related clinical phenotypes and with the effects of the disease-modifying 6-month training-intervention. Samples of vastus lateralis muscle (n = 12/13) and plasma (n = 20/21) were obtained from IIM patients and healthy controls, respectively. Muscle and plasma were obtained before and after a 6-month training-intervention in 7 patients. MyomiRs miR-1,-206,-133a,-133b were quantified by qPCR. Effects of pro-inflammatory (TNF), metabolic (glucose, insulin) systemic factors and the immunosuppressive therapy (dexamethasone) on the myomiRs were examined in muscle cells in vitro. MiR-133b was lower in skeletal muscle of IIM patients compared with healthy controls (p= 0.03). Levels of miR-133a, miR-1, and miR-206 were not regulated. Moreover, plasma levels of miR-133b and miR-1 were reduced in IIM compared with healthy controls (p< 0.05). Exercise induced reciprocal regulation of specific myomiRs in muscle and plasma of IIM patients, it lowered miR-133b in muscle while increasing miR-133b and miR-206 in plasma. Treatment of myotubes with TNF, insulin, and glucose and dexamethasone induced distinct myomiRs down-regulation. Lower myomiR levels in skeletal muscle of IIM patients might indicate reduced muscle regenerative potential in IIM, which could be linked to inflammation, metabolic dysfunction, and immunosuppressive therapy. Training-induced changes of muscle and plasma myomiRs indicate an increase in myomiRs release, which could contribute to the adaptive response underlying the positive systemic effects of exercise in IIM.

Changes in Levels of MiR-21, MiR-27a, MiR-221, and MiR-429 in the Thymus after Photodynamic Therapy and Surgical Treatment of Breast Cancer in Female Wistar Rats.

We studied the expression levels of microRNAs (miR-21, miR-27a, miR-221, and miR-429) in the thymus of female Wistar rats after surgical treatment of breast cancer (BC) and after photodynamic therapy for BC followed by tumor resection. In the group without treatment, the levels of pro-oncogenic miR-21, miR-27a, and miR-221 in the thymus were reduced in comparison with those in the group of intact control. After surgical treatment of BC, the levels of miR-21 and miR-27a in the thymus increased in comparison with those in BC without treatment. Surgical removal of the tumor followed by photodynamic therapy led to an even greater increase in the levels of miR-21 and miR-27a in the thymus in comparison with those in the group of surgical treatment alone. Expression of the tumor-suppressive miR-429 in the thymus significantly exceeds the levels in the BC without treatment and BC+surgery groups.

MiRNA-1 regulation is necessary for mechanical overload-induced muscle hypertrophy in male mice.

MicroRNAs (miRNAs) are small, noncoding RNAs that play a critical role in regulating gene expression post-transcriptionally. They are involved in various developmental and physiological processes, and their dysregulation is linked to various diseases. Skeletal muscle-specific miRNAs, including miR-1, play a crucial role in the development and maintenance of skeletal muscle. It has been demonstrated that the expression of miR-1 decreases by approximately 50% in response to hypertrophic stimuli, suggesting its potential involvement in muscle hypertrophy. In our study, we hypothesize that reduction of miR-1 levels is necessary for skeletal muscle growth due to its interaction to essential pro-growth genes. Promoting a smaller reduction of miR-1 levels, we observed a blunted hypertrophic response in mice undergoing a murine model of muscle hypertrophy. In addition, our results suggest that miR-1 inhibits the expression of Itm2a, a membrane-related protein, as potential miR-1-related candidate for skeletal muscle hypertrophy. While the exact mechanism in muscle hypertrophy has not been identified, our results suggest that miR-1-regulated membrane proteins are important for skeletal muscle hypertrophy.

Integrated analysis of long non‑coding RNA megacluster, microRNA‑132 and microRNA‑133a and their implications for cardiovascular risk and kidney failure progression in diabetic patients.

Inefficient control of elevated blood sugar levels can lead to certain health complications such as diabetic nephropathy (DN) and cardiovascular disease (CVD). The identification of effective biomarkers for monitoring diabetes was performed in the present study. The present study aimed to investigate the implications of long non-coding RNA megacluster (lnc-MGC), microRNA (miR)-132 and miR-133a, and their correlation with lactate dehydrogenase (LDH) activity and glycated hemoglobin (HbA1C) levels to identify biomarkers for the early diagnosis of diabetes mellitus, induced DN and CVD. The present study included a total of 200 patients with type 2 diabetes, as well as 40 healthy subjects as controls. The diabetic patients were classified into six groups based on their estimated HbA1c level, glomerular filtration rate and LDH activity, while the healthy controls constituted the seventh group. Diabetic patients exhibited significant increases in parameters related to diabetes as fasting blood sugar, HbA1c levels, cardiac injury and kidney failure. Furthermore, the expression levels of TNF-α were significantly increased in the diabetic groups compared with healthy controls. Diabetic patients with cardiovascular dysfunction showed significantly increased expression levels of miR-132, miR-133a and lnc-MGC, compared with the healthy group. The expression of circulating miR-132 in blood was low in the groups of diabetic patients compared with the healthy controls, and demonstrated a negative correlation with LDH and HbA1C levels. Expression levels of miR-132, miR-133a and lnc-MGC, along with their correlations with LDH and HbA1C levels, could be used to distinguish diabetic patients with reduced CVD from those at early stage diabetes, which indicated their potential as biomarkers for CV complications associated with diabetes mellitus in the future.

The diagnostic and predictive potential of lncRNA CASC2 targeting miR-155 in systemic lupus erythematosus patients with nephritis complication

Lupus nephritis (LN) is a serious problem that results from systemic lupus erythematosus (SLE) complications. Recent studies have highlighted that non-coding RNA (ncRNA) dysregulation is a notable feature in patients with SLE. As a result, this research was designed to investigate lncRNA CASC2 and miR-155 levels as non-invasive diagnostic biomarkers in SLE patients, including those with and without nephritis, and to investigate their effectiveness in assessing disease severity and predicting LN. Our study included 60 patients with SLE who were subclassified into (30 non-LN and 30 LN groups), along with 30 control subjects. Quantification of lncRNA CASC2 and miR-155 in serum samples from the Egyptian population was carried out with real-time polymerase chain reaction (RT-PCR). The disease activity index (SLEDAI) for SLE was evaluated, and the analysis of the receiver operating characteristic (ROC) curve was implemented. Increased levels of lncRNA CASC2 were observed in SLE patients compared to healthy controls, with even higher levels observed in the LN group versus the non-LN patients’ group. Conversely, miR-155 was noted to be down-regulated in SLE patients relative to controls, and its levels were lower in the LN group relative to the non-LN patients’ group. The elevated expression of lncRNA CASC2 and reduced expression of miR-155 were both correlated to the severity of the disease. The current study illustrated that both lncRNA CASC2 and miR-155 could act as valuable non-invasive diagnostic biomarkers for SLE and predicting LN among SLE patients, as well as their abilities to detect the disease severity and progression.

Circulating microRNAs as a Prognostic Tool to Determine Treatment Efficacy in Lung Cancer Patients Undergoing Pembrolizumab PD-1 Blockade Immunotherapy.

Background: Pembrolizumab has recently emerged as a PD-1 blockade immunotherapy treatment for lung cancer. It is critical that such treatment strategies for lung cancer should be chosen not only on the basis of histopathological features and the expression of targetable cell surface proteins (such as PD-1), but should rather be selected based on other determinants of treatment success or risk factors for poor prognosis. One method to forecast cancer trajectory is the identification of biomolecular signatures such as microRNAs (miRNAs), non-protein-coding RNA molecules that play a regulatory role in gene expression by modulating the translation or stability of messenger RNA. Methods: To find out which miRNAs have an important influence on anti-PD-1 treatment outcomes, we evaluated miRNA levels in sera from 38 lung cancer patients undergoing 3 months of pembrolizumab treatment. We selected a panel of miRNAs previously shown to be involved in lung cancer or PD-1 signaling and performed qPCR analysis. Results: Overall, we observed a significant decrease in the levels of miR126-5p (4-fold), let-7a (5-fold), miR133a-3p (4-fold), miR3615 (2-fold), miR4516 (3-fold), miR16 (3-fold), miR34c-5p (2-fold), miR20b-5p (5-fold), miR106b-5p (5-fold), miR146a-5p (3-fold) and miR181b-5p (3-fold) in response to treatment indicating effectiveness of immunotherapy. Within our selected panel of miRNAs, we identified two markers relevant to cancer prognosis: miR-217, which is negatively associated with patient survival, and let-7a, which is positively associated with patient survival. Conclusions: Our findings suggest that circulating miRNAs can be used for future treatment evaluation and lung cancer prognosis, with potential as therapeutic targets.

Unveiling Novel Biomarkers: A Clinical Study of miR-146a and miR-222 in the Diagnosis and Treatment of Polycystic Ovary Syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting 5%-10% of women of reproductive age. It is marked by hyperandrogenism, chronic anovulation, and polycystic ovarian morphology, with associated long-term health risks, including cardiovascular disease, type 2 diabetes, and infertility. This study investigates the potential of specific microRNAs, namely miR-146a and miR-222, as novel biomarkers for the diagnosis and treatment of PCOS. Materials and Methods: A structured, evidence-based approach was undertaken using real-time PCR to analyze the expression levels of miR-146a and miR-222 in Wistar albino rats with DHEA-induced PCOS. Blood samples were collected for RNA extraction and subsequent miRNA expression quantification. The diagnostic potential was evaluated through receiver operating characteristic (ROC) curve analysis of the expression data. Results: Both miR-146a and miR-222 showed upregulation in the PCOS group, compared to controls, though these differences were not statistically significant. ROC analysis indicated that miR-222 had a moderate discriminatory capability, with an area under the curve (AUC) of 0.70, supporting its potential as a biomarker for PCOS. miR-146a presented an AUC of 0.65, suggesting a less robust but relevant role in differentiating PCOS from control samples. Conclusion: The findings propose that miR-146a and miR-222 may serve as viable biomarkers for PCOS, facilitating the advancement of non-invasive diagnostic methods and targeted therapeutic options. Nevertheless, additional studies with larger sample sizes are essential to substantiate these preliminary findings.

Investigating miR-9 and miR-222 in CSF and Plasma of Neuroblastoma Patients as Metastatic and Apoptotic-Related Markers.

Neuroblastoma is a cancer that occurs due to abnormal development of the sympathetic nervous system. The dysregulation of miR-9 and miR-222 plays a crucial role in neuroblastoma development. These microRNAs have a significant relationship with PTEN, caspase-9, and MMP14, which can potentially form the basis for the specific diagnosis and treatment of this disease. In our study, two neuroblastoma cell lines were divided into three groups based on whether they had been treated with miR-9, anti-miR-9, miR-222, or both. We evaluated various parameters in these groups, including migration (through a wound healing assay), apoptosis (using flow cytometry), and gene expression (through qRT-PCR). Additionally, we measured the expression levels of MMP14, miR-9, and miR-222 in plasma and CSF samples from neuroblastoma patients using ELISA and qRT-PCR. We found that patients with neuroblastoma had higher levels of MMP14 and miR-222 mRNA expression but lower levels of miR-9 mRNA expression. Furthermore, after treating the cell lines with anti-miR-9 and anti-miR-222, we observed increased levels of MMP14 expression, as well as PTEN and caspase-9. Additionally, the treatment with anti-miR-222 and anti-miR-9 led to an increase in the frequency of apoptosis and migration of cancer cells. Our research shows that the dysregulation of miR-9, miR-222, and MMP14 could be key indicators in the pathogenesis of neuroblastoma. We also found that up-regulation of miR-9 was associated with decreased disease severity, whereas up-regulation of miR-222 and MMP14 was linked to increased disease severity.

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.

Tumor Suppressor miR-34a: Potential Biomarker of TACE Response in HCC.

TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12months after the first TACE. Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both sixmonths (FCa: p = 0.014) and 12months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. Level 3 Prospective cohort study.

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.

The Effect of Hybrid Blood Purification Combined with Ulinastatin for the Treatment of Severe Sepsis on APACHE II Score and Levels of miR-146a and miR-155.

Severe sepsis is a systemic inflammatory response syndrome caused by infection, and the Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) scoring system is widely used to assess the severity of severe patients. Hybrid blood purification treatment (HBPT) and ulinastatin (UTI) have shown good efficacy in a variety of inflammatory diseases, and miR-146a and miR-155 were found to be closely related to inflammatory reaction. The purpose of this study was to investigate the effect of HBPT combined with UTI in the treatment of patients with severe sepsis, especially the effects on APACHE II score and miR-146a and miR-155 levels. We carried out a retrospective analysis of clinical data with severe sepsis admitted to our hospital from January 2020 to June 2022. The patients were divided into an HBPT or HBPT+UTI group according to the treatment records. The APACHE II score, miR-146a level, miR-155 level, inflammatory factors, and rehabilitation status of both groups were analyzed and compared before and after treatment. A total of 150 were included in the analysis, there were 77 participants in HBPT+UTI and 73 in HBPT group. After treatment, the APACHE II score and levels of miR-146a, miR-155, and inflammatory factors were significantly lower than that before treatment. Furthermore, the HBPT+UTI group showed significantly lower values than the HBPT group (all P < 0.05). The recovery time of serum amylase, the disappearance time of abdominal pain, and the length of hospitalization in the HBPT+UTI group were significantly shorter than those in the HBPT group (all P < 0.05). UTI treatment combined with the administration of HBPT could improve the APACHE II score, alleviate the inflammatory reaction, and significantly improve the short-term prognosis of the patients with severe sepsis.

Correlations of Expression Levels of microRNA-206 and microRNA-186 in the Serum With Disease Severity and Prognosis of Elderly Patients With Vascular Dementia.

Objective To investigate the correlations of the expression levels of microRNA (miR)-206 and miR-186 in the serum with the disease severity and prognosis of elderly patients with vascular dementia (VD). Methods A total of 104 elderly patients with VD treated in Dalian Municipal Central Hospital from October 2020 to May 2023 were selected into the VD group and 104 healthy volunteers who underwent physical examinations were enrolled in the control group.Baseline data of both groups were collected,and fluorescence quantitative PCR was used to measure the expression levels of miR-206 and miR-186 in the serum.According to the severity of VD,the patients were assigned into mild,moderate,and severe VD groups.The elderly patients with VD were followed up for 6 months after discharge.According to the prognosis,the patients were assigned into good/moderate and poor prognosis groups.The baseline data and the serum levels of miR-206 and miR-186 were compared between the control and VD groups as well as between the good/moderate and poor prognosis groups.The serum levels of miR-206 and miR-186 were compared between the mild,moderate,and severe VD groups.The correlations of serum miR-206 and miR-186 levels with mini-mental state examination (MMSE) score in elderly patients with VD were analyzed,on the basis of which the factors affecting the poor prognosis of elderly patients with VD were predicated.Furthermore,the predictive values of serum levels of miR-206 and miR-186 on the poor prognosis of elderly patients with VD were evaluated. Results The VD group had higher proportions of diabetes history (P=0.021),hypertension history (P<0.001),and hyperlipidemia history (P<0.001),higher serum levels of miR-206 (P<0.001) and miR-186 (P<0.001),and lower score of activity of daily living (P<0.001) than the control group.The serum miR-206 and miR-186 levels varied between the mild,moderate,and severe VD groups (all P<0.001).The trend test results showed that serum miR-206 and miR-186 levels presented a rising trend in mild,moderate,and severe VD groups (all P<0.001).The serum miR-206 and miR-186 levels in elderly VD patients were negatively correlated with the MMSE score (all P<0.001).The poor prognosis group had lower MMSE score and higher serum levels of miR-206 and miR-186 than the good/moderate prognosis group (all P<0.001).The MMSE score was a protective factor and miR-206 and miR-186 were risk factors for poor prognosis in elderly patients with VD (P=0.005,P=0.001,P=0.007).The area under curve of combined serum miR-206 and miR-186 levels in predicting poor prognosis in the elderly patients with VD was 0.963,which was higher than those (0.866 and 0.878) of serum miR-206 and miR-186 levels separately (P=0.010,P=0.020). Conclusions The serum levels of miR-206 and miR-186 in elderly patients of VD are high and closely related to the severity and prognosis of VD.The combination of the two demonstrates high performance in predicting the prognosis of elderly patients with VD.

Mechanism of ginsenoside Rg_1 in regulating autophagy through miR-155/Notch1/Hes1 pathway to attenuate hypoxia/reoxygenation injury in HL-1 cells

This article explored the specific mechanism by which ginsenoside Rg_1 regulates cellular autophagy to attenuate hypoxia/reoxygenation(H/R) injury in HL-1 cardiomyocytes through the microRNA155(miR-155)/neurogenic gene Notch homologous protein 1(Notch1)/hairy and enhancer of split 1(Hes1) pathway. An HL-1 cell model with H/R injury was constructed, and ginsenoside Rg_1 and/or Notch1 inhibitor DAPT and miR-155 mimics were used to treat cells. Cell counting kit(CCK)-8 was used to detect the relative viability of HL-1 cells with H/R injury. The lactate dehydrogenase(LDH) content in cell culture medium supernatant was detected by using an LDH assay kit, and autophagosome in cells was observed by transmission electron microscopy. The level of autophagy in cells was detected through the mono-dansyl-cadaverine(MDC) detection method. Fluorescence quantitative polymerase chain reaction was used to detect the mRNA levels of miR-155, Notch1, Hes1, and microtubule-associated protein1 light chain 3(LC3), and Western blot was used to detect the protein expression levels of Notch1, Hes1, LC3Ⅰ, and LC3Ⅱ. The results show that after H/R injury, the activity of HL-1 cells decreases, and LDH leakage increases. Besides, the number of intracellular autophagosomes increases, and the mRNA level of LC3 and the LC3Ⅱ/LC3Ⅰ ratio are elevated. In addition, ginsenoside Rg_1 can increase cell activity, decrease LDH leakage and the number of intracellular autophagosomes, and reduce the mRNA level of LC3 and the LC3Ⅱ/LC3Ⅰ ratio. Therefore, it plays a cardioprotective role by inhibiting autophagy, and Notch1 inhibitor or miR-155 overexpression can inhibit the effect of ginsenoside Rg_1, promote autophagy, and aggravate H/R injury in HL-1 cells. Ginsenoside Rg_1 can inhibit the reduction of Notch1 and Hes1 mRNA levels and protein expressions and the increase in miR-155 mRNA levels caused by H/R injury, while Notch1 inhibitors or miR-155 overexpression show the opposite effect. In summary, ginsenoside Rg_1 can regulate autophagy through the miR-155/Notch1/Hes1 pathway to alleviate H/R injury in HL-1 cardiomyocytes.

MiR-1, miR-133a, miR-29b and skeletal muscle fibrosis in chronic limb-threatening ischaemia.

Chronic limb-threatening ischaemia (CLTI), the most severe manifestation of peripheral arterial disease (PAD), is associated with a poor prognosis and high amputation rates. Despite novel therapeutic approaches being investigated, no significant clinical benefits have been observed yet. Understanding the molecular pathways of skeletal muscle dysfunction in CLTI is crucial for designing successful treatments. This study aimed to identify miRNAs dysregulated in muscle biopsies from PAD cohorts. Using MIcroRNA ENrichment TURned NETwork (MIENTURNET) on a publicly accessible RNA-sequencing dataset of PAD cohorts, we identified a list of miRNAs that were over-represented among the upregulated differentially expressed genes (DEGs) in CLTI. Next, we validated the altered expression of these miRNAs and their targets in mice with hindlimb ischaemia (HLI). Our results showed a significant downregulation of miR-1, miR-133a, and miR-29b levels in the ischaemic limbs versus the contralateral non-ischaemic limb. A miRNA target protein-protein interaction network identified extracellular matrix components, including collagen-1a1, -3a1, and -4a1, fibronectin-1, fibrin-1, matrix metalloproteinase-2 and -14, and Sparc, which were upregulated in the ischaemic muscle of mice. This is the first study to identify miR-1, miR-133a, and miR-29b as potential contributors to fibrosis and vascular pathology in CLTI muscle, which supports their potential as novel therapeutic agents for this condition.

Abstract A007: Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients

Abstract Background: Prostate cancer (PCA) is the second most prevalent cancer globally and the fifth leading cause of cancer-related mortality. However, effective prognostic biomarkers for metastatic PCA remain lacking. Recent research highlights the role of microRNAs (miRNAs) in regulating cancer stem cells (CSCs) and influencing tumour progression across various cancers. Therefore, in this we investigated the effects of miR-141 and miR-145 expression on the metastatic PCA of CSCs and assessed their potential role as biomarkers for metastatic PCA prognosis. Methods: The expression levels of miR-141 and miR-145 were quantified using real-time qPCR. Flow cytometry was employed to assess the levels of prostate cancer stem cells (PCSCs) in tissue samples from patients with localized (non-metastatic) and metastatic PCA. Results: Our findings revealed a significant increase in miR-141 expression, accompanied by elevated levels of CD44^high/CD24^low and CD133^high, in metastatic PCA compared to localized PCA. Conversely, reduced miR-145 expression was associated with enhanced stemness characteristics, as indicated by increased CD44^high/CD24^low and CD133^high levels, in metastatic PCA compared to localized PCA. Additionally, prostate-specific antigen (PSA) and testosterone levels exhibited a significant rise (p&amp;lt;0.001), while apoptosis rates decreased in both localized and metastatic PCA compared to localized PCA. Conclusions: The collective findings of this study suggest that miR-141 and miR-145, in conjunction with CSC markers, hold promise as diagnostic and prognostic tools for PCA. They may also be valuable for detecting minimal residual disease and improving therapeutic strategies for managing metastatic PCA. Citation Format: Kamla Kant Shukla, Gautam Ram Choudhary. Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A007.

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.