Serum miR-21 Research Articles

Expression of miR-22 profiling in colorectal normal-adenoma-carcinoma sequence

Colorectal cancer (CRC) is the third most common cancer in the world. MiRNA-22 has emerged as a potential candidate with diagnostic significance; however, its expression profile across the normal-adenoma-carcinoma transition in colorectal remains unexplored. In this study, we evaluated serum miRNA-22 levels in patients with varying stages of CRC. The study cohort comprised 49 healthy controls, 50 patients with polyps, 51 individuals with colorectal adenoma (CRA), and 50 cases of CRC, confirmed through proctocolonoscopy and pathological biopsy. Real-time quantitative polymerase chain reaction was employed to validate the significantly differential expression of serum miRNA-22 among different stages of CRC progression. The 2-ΔΔCT method was utilized to assess the relative changes in serum miRNA-22 expression levels. Our results revealed no significant differences in gender, adenoma grade, location, or TNM classification stage in terms of serum miR-22 expression across the four groups. Notably, both the CRC and CRA groups exhibited higher miR-22 expression levels compared to the control group (p = 0.0001, p = 0.0004), with the CRA and CRC groups displaying higher expression levels than the polyp group (p = 0.02, p = 0.043). Ordered multicategorical logistic regression analysis model revealed the utilization of age, gender, smoking status, and miR-22 expression collectively exhibited the highest value for the area under the curve (AUC = 0.748) in the discrimination between individuals CRC and healthy. The independent factor of expression of miR-22 demonstrated the most notable predictive capacity (AUC = 0.753) when distinguishing between CRA and healthy individuals. Furthermore, the independent expression of miR-22 exhibited discernible potential (AUC = 0.654, 0.636) differentiation between polyps and CRA/ CRC. Notably, the factor of age displayed the most substantial discriminatory power (AUC = 0.741) when distinguishing between polyps and healthy individuals. Our findings provide supportive evidence for considering miR-22 as a potential biomarker for CRC early screening. Nonetheless, the molecular mechanisms of miR-22 regulation in colorectal lesions still need to be investigated.

Serum miRNA-21, miRNA-146a and plasma cell free DNA as novel biomarkers for assessing systemic lupus erythematosus activity

BackgroundMicroRNA and cell-free DNA have shown significant correlations with several autoimmune disorders including systemic lupus erythematosus (SLE). SLE has been associated with challenges in determining its activity, so that the need for biomarkers contributing to assessing its activity is emerging. The current study investigated miRNA-21, miRNA-146a and plasma cf-DNA in determination of SLE activity, in addition their association with clinical data including complement factor 3 (C3), complement factor(C4), anti-dsDNA, and other disease activity indices.Methods and resultsEighty subjects divided into; twenty active patients (with SLE-DAI2K score of 16–18) twenty inactive patients (with SLE-DAI2K score of 1–3), and forty healthy control participants) were included in this study. Serum miR-21, miR-146a, and plasma cf-DNA were quantified by real time PCR and their correlation with clinical data was statistically analyzed. The results demonstrated that active cases have significant upregulation of serum miRNA-21 and plasma cf-DNA. Moreover, miR-21 showed a negative, significant pertaining to C3, C4 and was positively related to Systemic Lupus Erythematosus Disease Activity Index 2 K score (SLE-DAI Index2K score) and Systemic-Lupus-Erythematosus-Disease Activity-Index 2 K activity (SLE-DAI 2 K activity). Also, Active group miRNA-146a was negatively, significantly correlated with C3, as well as a positive significant relationship with SLE-DAI2K score and SLEDAI 2 K activity, in addition to anti DNA Autoantibodies. Furthermore, miR-21 and cf-DNA demonstrated a differential value through Receiver Operating Characteristic (ROC) curve’s study.Conclusionsthe present study illustrated miR-21, miR-146a, and cf-DNA relationship with SLE clinical data. In addition to their potential value in SLE diagnosis, and activity determination.

Clinical role of serum microRNA-155 in early diagnosis and prognosis of septic patients with acute kidney injury.

Acute kidney injury (AKI) is a common complication in patients with sepsis, and early detection and timely treatment are crucial. This article aims to explore the clinical role of microRNA-155 (miR-155) in early diagnosis and prognosis evaluation of septic patients with acute kidney injury. We collected the blood samples of septic patients and measured the relative expression of serum miR-155 by RT-qPCR, and drew the receiver operating characteristic (ROC) curves to evaluate its early diagnosis for septic AKI. The relative expression of miR-155 in the septic AKI was significantly higher than that in the septic non-AKI, and increased with the aggravation of renal function damage. The ROC curve of miR-155 for the diagnosis of septic AKI was 1.91 (95% CI: 1.61-2.19). When the optimal cut-off value of miR-155 expression was 2.37, its sensitivity for diagnosing septic AKI was 91.12% (95% CI: 80.41-95.07%), and its specificity was 84.52% (95% CI: 71.74-89.36%). Furthermore, the severity of kidney injury, SOFA score, APACHE II score and miR-155 were the risk factors affecting the prognosis of septic patients with AKI. Serum miR-155 can be used as a novel biomarker for the early diagnosis of septic AKI, and also has important clinical value in the prognosis evaluation of septic patients with AKI.

Differential expression of serum miR-486 and miR-25 in ulcerative colitis and Crohn’s disease: Correlations with disease activity, extent, and location

Novel reliable biomarkers of inflammatory bowel disease (IBD) are clinically imperative due to potential limitations of endoscopic techniques. MicroRNAs (miRNAs) have emerged as non-invasive biomarkers of IBD; however, the full disease-specific miRNAs signature for IBD subtypes remains elusive. We evaluated the diagnostic role of circulating miR-486 and miR-25 in IBD patients and their potential ability to discriminate IBD subtypes; ulcerative colitis (UC) and Crohn’s disease (CD). Sixty UC patients, 60 CD patients, and 60 healthy controls were recruited. Serum miRNA expression was determined using RT-qPCR. Bioinformatics was employed for target gene and protein-protein interaction (PPI) network analyses. Serum miR-486 was upregulated in CD patients, but didn’t change in UC patients compared to controls. Conversely, serum miR-25 was decreased in both CD and UC patients compared to controls. Only miR-486 was differentially expressed between UC and CD patients. Receiver-operating characteristic analysis revealed that serum miR-486 was superior in CD diagnosis (AUC=0.945) and significantly distinguished CD and UC patients, whereas miR-25 showed discriminative potential for both UC and CD from controls. In the multivariate logistic analysis only miR-486 was associated with the risk of CD diagnosis. Serum miR-486 was correlated with CD activity index and location of disease in CD patients, whereas miR-25 was correlated with the type/extent of UC. PPI network analysis revealed common target genes and signaling pathways for both miRNAs. Conclusively, serum miR-486 and miR-25 might serve as new biomarkers of IBD, with serum miR-486 could be employed in risk stratification of IBD subtypes and has the ground for clinical utility in CD diagnosis, whereas miR-25 has potential for UC and CD diagnosis.

Are Vascular Endothelium and Angiogenesis Effective MicroRNA Biomarkers Associated with the Prediction of Early-Onset Preeclampsia (EOPE) and Adverse Perinatal Outcomes?

MicroRNA is associated with angiogenesis, invasion, proliferation, and vascular endothelial remodeling of various diseases. We aimed to investigate serum MicroRNA (miRNA) levels in preeclampsia (PE) and to determine whether any changes in miRNA levels are useful in predicting early onset preeclampsia (EOPE) and adverse perinatal outcomes. A total of 89 pregnant patients were enrolled in this prospective case-control study (55 PE and 34 healthy controls). miR-17, miR-20a, miR-20b, miR126, miR155, miR-200, miR-222, and miR-210 levels were studied in maternal serum in preeclamptic pregnant women. Multiple logistic regression analyses analyzed the risk factors which are associated with EOPE and adverse maternal outcomes. The Real-time RT-PCR method was used to determine maternal serum miRNA levels. Serum miR-17, miR-20a, miR-20b, miR126, and miR-210 levels were significantly higher in PE than the control group (p < .001, p < .001, p < .001, p < .001 and p = .047 respectively). Increased miR-17, miR-20a, and miR-20b levels were independently associated with PE (OR: 0.642, 95%Cl: 0.486-0.846, p = .002; OR: 0.899, 95%Cl: 0.811-0.996, p = .042 and OR: 0.817, 95%Cl: 0.689-0.970, p = .021). Increased miR-17 and miR-126 levels were negatively correlated with serum EOPE in PE (r = -.313, p = .020), and increased miR-210 levels were significantly positively correlated with EOPE in PE (r = .285, p = .005). Increased expression of serum miR-17, miR-20a, miR-20b, miR126, and miR-210 were found to be associated with PE, also increased expression of miR-17, miR-20a, and miR-20b were to be predicted with PE, also increased maternal serum miR-17 and miR-126 expressions were negatively correlated and increased miR-210 expression was positively correlated with EOPE in PE women.

Prognostic utility of MicroRNA-221 and interleukin-6 in cerebral ischemic stroke

Cerebral ischemic stroke has a significant mortality rate and persistent impairment. The initial diagnosis of stroke occurs by magnetic resonance imaging and computed tomography. There is a strong need for more accessible, less expensive, and non-invasive methods besides the neuroimaging methods. MicroRNAs (miRNAs) are critical regulators for ischemic stroke as they are involved in stroke pathophysiology. The goal of the current study was to determine whether microRNA-221 (miR-221) could be used as a diagnostic biomarker for patients with ischemic stroke, and whether it can serve as a promising indicator of the disease severity especially if combined with interleukin-6 (IL-6). The study included 90 subjects, 45 cerebral ischemic stroke patients and 45 controls. MiR-221 was evaluated by quantitative real-time polymerase chain reaction (q-PCR) and IL-6 by enzyme-linked immunosorbent assay (ELISA). Our study results revealed that the serum miR-221 level was significantly reduced in cerebral ischemic stroke patients when compared to the control group (p&lt;0.0001). In addition, serum miR-221 showed a significant negative correlation with cerebral stroke severity (p&lt;0.0001), whereas serum IL-6 showed a significant positive correlation with cerebral stroke severity (p &lt; 0.0001). We also analyzed the receiver operator characteristic (ROC) curve and found that area under the ROC curve (AUC) for severity of ischemic stroke by miR-221 was 0.97 (95% confidence intervall0.93–1, p&lt;0.001). Notably, the combination of serum miR-221 with IL-6 for prediction of ischemic stroke severity showed both increased sensitivity/specificity (AUC=0.99, 95% confidence interval 0.96-1, p&lt;0.001) than miR-221 alone. We concluded that miR-221 constituted a non-invasive, sensitive, and specific biomarker that could be used for diagnosis of ischemic stroke and for prediction of its severity.

Suppression of mir-150–5p attenuates the anti-inflammatory effect of glucocorticoids in mice with ulcerative colitis

Glucocorticoids have been widely used in the treatment of ulcerative colitis, but not all patients benefit from this therapy due to hormone resistance. Mir-150–5p has been reported to enhance the efficacy of glucocorticoids, and low serum mir-150–5p expression has been linked to glucocorticoid resistance in ulcerative colitis patients. The aim of this study was to elucidate the mechanisms of mir-150–5p regulation on glucocorticoid resistance. An ulcerative colitis mouse model was used to evaluate changes in ulcerative colitis symptoms, inflammatory factors, and glucocorticoid resistance-related gene expression. The results showed that mir-150–5p suppression with antagomirs did not significantly interfere with or enhance the induction of ulcerative colitis symptoms by dextran sulfate sodium, but it did attenuate the inflammation inhibitory effect of dexamethasone by abnormally regulating the expression of IL-17a, IL-10, IL-2 and IL-6 levels and myeloperoxidase activity. Mir-150–5p inhibition also induced a glucocorticoid-resistant gene expression profile in colon tissues of ulcerative colitis mice, with upregulation of p-ERK, p-JNK, and HSP90 and downregulation of p-GRa, FKBP4, and HDAC2 expression. Our results indicate that mir-150–5p suppression attenuates the anti-inflammatory effect of glucocorticoids and may function as a driver element in ulcerative colitis glucocorticoid resistance. Availability of data and materialsAll data and figures analyzed in this study are available from the corresponding author by request.

Circulating and Cardiac Tissue miRNAs in Children with Dilated Cardiomyopathy.

microRNAs (miRs) are small non-coding single-stranded RNAs that regulate gene expression. We previously evaluated expression of miRs in the cardiac tissue of children with dilated cardiomyopathy (DCM) using miRNA-seq. However, a comparative analysis of serum and cardiac miRs has not been performed in this population. The current study aimed to evaluate miR levels in the serum of pediatric DCM patients compared to healthy non-failing (NF) donor controls and investigate the association between miR levels in tissue and sera from the same pediatric DCM patients. Defining the relationship between serum and tissue miRs may allow the use of circulating miRs as surrogate markers of cardiac miRs. miR levels were investigated through miR-array in sera [n = 10 NF, n = 12 DCM] and miR-seq in tissue (n = 10 NF, n = 12 DCM). Pathway analysis was investigated using the miR enrichment analysis and annotation tool (miEAA) for the five miRs commonly dysregulated in the sera and tissue of pediatric DCM patients. Functional analysis of miRs commonly dysregulated in the sera and tissue of pediatric DCM patients suggests altered pathways related to cell growth, differentiation and proliferation, inflammation, mitochondrial function, and metabolism. These findings suggest that circulating miRs could reflect altered levels of cardiac tissue miRs.

A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study.

Saliva and serum miR-21, miR-136, miR-3928, and miR-29B, are potentially associated with oral cancer even at an early stage, especially miR-21 in individuals with a smoking history, a further validation in a larger cohort of subjects with premalignant and early malignant lesions need to confirm.

Predictive Role of Pretreatment Circulating miR-221 in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Aberrantly expressed circulating microRNAs (miRNAs) have been demonstrated to have a crucial role in the diagnosis and prognostication of various cancers, including hepatocellular carcinoma (HCC). This research aimed to examine the role of specific miRNAs in predicting the outcomes for individuals with hepatitis B virus (HBV)-related HCC treated with transarterial chemoembolization (TACE). Stored serum specimens collected prior to the first TACE procedure were employed to determine the expression of serum miR-122, miR-221, and miR-224 using quantitative real-time PCR analysis. The study included 100 HCC patients (84% males, with an average age of 60 years) who were treated with TACE. Throughout the median follow-up spanning 18.5 months (within a range of 3 to 60 months), 42 (42.0%) patients met the criteria of TACE refractoriness. Through multivariate analysis, elevated expressed miR-221 (≥4.0 log10 copies) and advanced HCC staging were identified as independent factors related to TACE refractoriness and short overall survival. However, serum miR-122 and miR-224 levels were not linked to treatment response or overall survival. These findings underscored the potential of incorporating pretreatment levels of serum miR-221 into the established tumor staging to enhance the accurate assessment of TACE responsiveness and prognostic outcome of patients with HCC.

Changes and Clinical Value of Serum miR-24 and miR-223 Levels in Patients with Severe Pneumonia.

Severe pneumonia progresses rapidly, so early assessment of the severity and prognosis is crucial for reducing mortality rates. We explore the role of serum microRNA-24 (miR-24) and microRNA-223 (miR-223) in the prognosis of severe pneumonia. There were a total of 96 patients with general pneumonia, 94 patients with severe pneumonia, and 93 healthy people, who were enrolled in this study. The levels of serum miR-24 and miR-223 were detected by real-time fluorescent quantitative PCR in all groups. The serum miR-223 level in the severe group was higher than that in the common group and the control group, and the miR-24 level was lower than that in the common group and the control group (P<0.05). The serum miR-223 levels and APACHEII scores in the death group were higher than those in the survival group on the first, third, and seventh day after admission, while the miR-24 levels were lower than those in the survival group (P<0.05). The proportion of patients with mechanical ventilation in the death group was higher than that in the survival group (P<0.05). The level of serum miR-24 was negatively correlated with APACHEII score and mechanical ventilation in patients who died of severe pneumonia (P<0.05), and miR-223 was positively correlated with APACHEII score and mechanical ventilation (P<0.05). The AUC predicted by serum miR-24, miR-223, and APACHEII scores alone and jointly were 0.867, 0.839, 0.791, and 0.952, respectively. MiR-24 and miR-223 are protective and independent risk factors for mortality in severe pneumonia patients, respectively (P<0.05). MiR-24 was a protective factor affecting the death of patients with severe pneumonia, and miR-223 was an independent risk factor affecting the death of patients with severe pneumonia (P<0.05). The combination of serum miR-24 and miR-223 levels on the first day after admission and APACHEII score can effectively predict prognosis.

The Ratio of miR-122 to miR-20a (miR-122/miR-20a) Is a Useful Minimally Invasive Biomarker for Non-Alcoholic Fatty Liver Disease Detection.

Background: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has become a global health problem. NAFLD has few initial symptoms and may be difficult to detect early, so there is need for a minimally invasive early detection marker. We hypothesized that miR-122 and miR-20a levels combined, as the miR-122/miR-20a ratio might detect NAFLD more sensitively. Methods: This study involved 167 participants with low alcohol intake. Those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 44), which was further classified into mild (n = 26) and severe (n = 18) groups based on echogenic intensity and hepatic vessel and diaphragm visualization. Participants without fatty liver were included in the normal group, except for those with an abnormal body mass index, glycated hemoglobin, and systolic blood pressure (n = 123) values. Serum miR-122 and miR-20a expression levels in participants were measured by real-time polymerase chain reaction, and the miR-122/miR-20a was calculated. Results: In the NAFLD group, miR-122 expression was significantly higher and the miR-20a was significantly lower than in the normal group, in agreement with previous studies. miR-122/miR-20a was also significantly higher in the NAFLD group. Receiver operating characteristic curve analysis was performed with miR-122/miR-20a as an NAFLD detection marker, and the area under the curve of miR-122/miR-20a was significantly larger than that of miR-122 or miR-20a alone. Conclusions: The miR-122/miR-20a ratio, combined with miR-122 and miR-20a levels, is a useful biomarker to detect NAFLD with high sensitivity.

Retracted: Clinical Value Analysis of Xiaozheng Decoction Combined with Bladder Perfusion for Postoperative Treatment of Bladder Cancer and Its Effect on Serum miR-143 and miR-92a.

[This retracts the article DOI: 10.1155/2022/8177674.].

Association of serum miR-375, miR-155 and miR-146b levels with distinguish of papillary thyroid cancer from benign thyroid masses among Iranian patients

Background and aimCertain serum levels of microRNAs (miRNAs) throughout the body can be helpful for cancer diagnosis and prognosis. The miRNAs can be secreted from the papillary thyroid cancer (PTC) into the circulatory system. Accordingly, this study aimed to measure the serum levels of miR-146b, miR-155 and miR-375 to evaluate their diagnostic potentials in distinguish of benign from malignant lesions.Materials and methodsThe serum levels of miRNAs were measured by real-time quantitative RT-PCR among100 patients with benign thyroid nodules and 30 patients with PTC.ResultsThe mean miR-375 and miR-155 expression levels in the PTC group were greater when compared with the benign group. The area under the ROC curve (AUC) was estimated at 0.81 for the miR-375 with 0.76% sensitivity and 0.80% specificity to distinguish between benign and PTC lesions. The AUC was calculated to be 0.75 for the miR-155 with 0.69% sensitivity and 0.90% specificity.ConclusionAccording to the results of this study, the serum levels of miR-155 and miR-375 were increased in the patients with PTC, which may be useful as alternative seromarkers for the PTC.

Therapeutic effects and safety of apatinib mesylate on patients with gastric carcinoma peritoneal metastasis in SOX scheme.

The aim of this study was to investigate the diagnostic values of serum tumor markers in gastric carcinoma peritoneal metastasis and the therapeutic efficacy as well as safety of apatinib mesylate combined with Geo+Oxaliplatin (SOX) scheme treatment in gastric carcinoma peritoneal metastasis. Sixty patients with gastric carcinoma peritoneal metastasis and 11 patients without gastric carcinoma peritoneal metastasis were selected as the research subjects. The levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9] and abdominal irrigating solution exosome [micro ribonucleic acid (miR)-21 and miR-320c] and the differences in their diagnostic values were compared and analyzed. The patients with gastric cancer peritoneal metastases are then divided into two groups, one for control (30 cases receiving just SOX scheme treatment) and the other for the experiment (30 cases receiving SOX scheme treatment plus apatinib mesylate). Besides, the differences in serum tumor marker level, therapeutic efficacy, overall survival (OS), complication rating, and Quality of Life Questionnaire-Core-30 (QLQ-C30) score among patients after treatment were compared. Demonstrated that serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9 levels of patients in the transfer group were remarkably enhanced compared with those of patients in the non-transfer group, and the levels of abdominal irrigating solution exosome (miR-21 and miR-320c) were reduced compared with those in non-transfer group (p<0.05). The area under the curve (AUC) of the diagnosis of gastric carcinoma peritoneal metastasis by each index were 0.553, 0.880, 0.832, 0.619, 0.863, 0.651, 0.918, and 0.903, respectively. Patients in the experimental group's serum levels of CEA, CA125, CA211, CA242, CA724, and CA19-9 were noticeably lower after therapy compared to those in the control group, and their median OS was also noticeably longer (p<0.05). After treatment, the objective remission rate (ORR) and disease control rate (DCR) of the control group and experimental group amounted to 6.7% vs. 30.0% and 50.0% vs. 86.7%, respectively. ORR and DCR of the experimental group were notably higher (p<0.05). Between the patients in the control group and the experimental group, there were no glaring variations in the frequency of problems (hypertension, nausea, vomiting, bone marrow suppression, hand-foot syndrome, and leucopenia) (p>0.05). The cognitive function, emotional function, and life health scores of patients in the experimental group were significantly higher than those in the control group (p<0.05), which suggested that serum tumor markers and miR-21 as well as miR-320c showed high diagnostic efficiency in gastric carcinoma peritoneal metastasis. Apatinib mesylate combined with SOX scheme treatment was more effective in treating gastric carcinoma peritoneal metastasis and possessed the same safety as single SOX scheme treatment. Hence, it is worthy of clinical promotion.

Phosphorus May Induce Phenotypic Transdifferentiation of Vascular Smooth Muscle Cells through the Reduction of microRNA-145.

Phosphorus is a vital element for life found in most foods as a natural component, but it is also one of the most used preservatives added during food processing. High serum phosphorus contributes to develop vascular calcification in chronic kidney disease; however, it is not clear its effect in a population without kidney damage. The objective of this in vivo and in vitro study was to investigate the effect of high phosphorus exposure on the aortic and serum levels of miR-145 and its effect on vascular smooth muscle cell (VSMCs) changes towards less contractile phenotypes. The study was performed in aortas and serum from rats fed standard and high-phosphorus diets, and in VSMCs exposed to different concentrations of phosphorus. In addition, miR-145 silencing and overexpression experiments were carried out. In vivo results showed that in rats with normal renal function fed a high P diet, a significant increase in serum phosphorus was observed which was associated to a significant decrease in the aortic α-actin expression which paralleled the decrease in aortic and serum miR-145 levels, with no changes in the osteogenic markers. In vitro results using VSMCs corroborated the in vivo findings. High phosphorus first reduced miR-145, and afterwards α-actin expression. The miR-145 overexpression significantly increased α-actin expression and partially prevented the increase in calcium content. These results suggest that miR-145 could be an early biomarker of vascular calcification, which could give information about the initiation of the transdifferentiation process in VSMCs.

Roles of microRNA-192 in diabetic nephropathy: the clinical applications and mechanisms of action.

Diabetic nephropathy (DN) is one of the most common and intractable microvascular complications of diabetes worldwide, serving as the main cause of terminal renal disease. Due to the lack of early specific symptoms and diagnostic markers, DN severely threatens the sufferer's life. MicroRNA-192 (miR-192) was early identified in human renal cortical tissue and stored and excreted in urine as microvesicles. MiR-192 was found to be involved in the development of DN. For the first time, the present review summarized all the current evidence on the topic of the roles of miR-192 in DN. Finally, 28 studies (ten clinical trials and eighteen experimental studies) were eligible for thorough reviewing. Most of the clinical trials (7/10, 70%) indicated miR-192 might be a protective factor for DN development and progression, while the majority of experimental studies (14/18, 78%) suggested miR-192 might be a pathogenic factor for DN. Mechanistically, miR-192 interacts with various direct targeted proteins (i.e., ZEB1, ZEB2, SIP1, GLP1R, and Egr1) and signaling cascades (i.e., SMAD/TGF-β and PTEN/PI3K/AKT), together contribute to the pathogenesis of DN through epithelial-to-mesenchymal transition (EMT), extracellular matrix deposition, and fibrosis formation. The current review highlights the dual role of miR-192 in the development of DN. Low serum miR-192 expression could be applied for the early prediction of DN (the early stage of DN), while the high miR-192 level in renal tissues and urine may imply the progression of DN (the late stage of DN). Further investigations are still warranted to illustrate this inconsistent phenomenon, which may facilitate promoting the therapeutic applications of miR-192 in predicting and treating DN.

#5629 EFFECT OF HIGH PHOSPHORUS CONTENT/DIET ON MIR-145 LEVELS AND VASCULAR SMOOTH MUSCLE CELLS OSTEOGENIC DIFFERENTIATION

Abstract Background and Aims Phosphorus (P) is found in most foods as a natural component, but nowadays, with the rise in the consumption of processed foods, P intake has increased in the developed world. Elevated serum P in patients with chronic kidney disease (CKD) contributes to development of vascular calcification. However, it is poorly understood the relationship between high P dietary intake and vascular calcification in healthy population with normal renal function, and the molecular pathways responsible for the transdifferentiation of vascular smooth muscle cells (VSMCs) that precedes it. Recent studies show that miR-145 is the most abundant microRNA (miR) in VSMCs, and its decrease is associated with loss of contractile phenotype -lower α-actin levels- and increased osteogenic differentiation. In addition, low serum levels of miR-145 has been associated with the presence of vascular calcification. Thus, the aim of the study was to evaluate the effect of high P dietary intake on aortic and serum miR-145 levels, phenotypic alterations of VSMCs and vascular calcification. Method The study was performed: a) in vivo in aortas and serums from rats with normal renal function fed normal P (NP, 0,6% P -n = 10-) and high P diets (HP, 0,9% P -n = 10-), and b) in vitro exposing the VSMCs to different concentrations of P (up to 3 mM), and overexpressing and silencing miR-145 to investigate its potential role in the VSMCs phenotypic differentiation. Results a) In vivo study: The HP group showed higher serum P (NP: 1.29 [1.15-1.35] vs HP:1.40 [1.33-1.48] mmol/L, p = 0.02) and PTH levels (NP: 235.58 ± 75.58 vs HP: 498.67 ± 142.07 pg/ml, p = 0.0001), without significant differences in serum Ca and FGF23 levels. There were not differences in aortic Ca content, although there was a significant reduction in α-actin expression in the HP group (NP: 2.49 [2.10-3.25] vs HP:1.23 [1.04-1.50] R.U., p = 0.002). Moreover, the aortic and serum levels of miR-145 were lower in the HP group: aortic miR-145 (NP: 1.26 [0.97-1.49] vs HP: 0.56 [0.38-0.69] R.U., p = 0.004) and serum miR-145 (NP: 0.84 [0.70-0.99] vs HP: 0.37 [0.31-0.52] R.U., p = 0.001). b) In vitro study: A7r5 cells exposure to high P reduced miR-145 (1mM P: 1.00 [0.88-1.28] vs 3mM P: 0.41 [0.32-0.52], p = 0.001), and α -actin (1mM P: 1.03 [0.96-1.15] vs 3mM P: 0.73 [0.61-0.74], p = 0.0008) levels increasing Ca content in a P concentration-dependent manner (1 mM P: 0.24 [0.00-1.17]; 1.5 mM P: 0.66 [0.47-2.61]; 2 mM P: 2.72 [1.06-4.01]; 2.5 mM P: 4.60 [3.02-4.91]; 3 mM P: 5.81 [5.58-6.34], p = 0.000). the silencing of miR-145 under standard P content (1mM), decreased α -actin (control: 1.02 [0.99-1.04] vs miR-145 antagomir: 0.75 [0.69-0.90] R.U., p = 0.0007), meanwhile its overexpression increased it (control: 1.02 [0.99-1.04] vs miR-145 mimic: 2.70 [2.68-3.07] R.U., p = 0.001). The α -actin levels and Ca content were not modified after silencing miR-145 under high P conditions C (3 mM), meanwhile miR-145 overexpression under high P conditions increased α -actin levels (control: 0.54 [0.41-0.61] vs miR-145 mimic: 1.82 [1.68-2.04] R.U., p = 0.0005), and partially prevented the increases in Ca content (control: 182.77 [176.78-194.84] vs miR-145 mimic: 117.16 [112.27-122.69] R.U., p = 0.0005). Conclusion The results indicate the high P exposure could lead to an impairment of vascular health by causing decrease in miR-145 levels with the consequent reduction in α -actin expression in VSMC cells.

Dual-model photoelectrochemical biosensor via DNAzyme walker integrated nanoprobe for ultrasensitive ratiometric detection of microRNA-155

Ultrasensitive detection for low concentration and abnormal expression of microRNA-155 (miR-155) in serum (fM level) at the early stage of cancer still exist great challenges. Therefore, a dual-model photoelectrochemical biosensor was developed based on label-free trimetallic nanoprobe and Mg2+ dependent DNAzyme driven DNA walker to generate ratiometric dual-signal output for sensitive biosensing of miR-155 from breast cancer cells (MCF-7) and cervical cancer cells (HeLa). In signal amplification strategy, PtCo@Prussian Blue nanozyme was selected as a signal nanoprobe with high catalytic activity and large specific surface area, while two dimensional MXene/AuNPs as surface modification material was applied to improve the active sites of the electrode. With the presence of the target, the DNAzyme assisted DNA walker process was initiated and abundant signal nanoprobe was introduced to the electrode surface, producing high current response and weak ultraviolet-visible spectrophotometry (UV–vis) response. Hence, the biosensor for miR-155 shows a low limit of detection of 1.2 fM from the linear range of 5 fM to 5 nM, exhibiting excellent stability and reproducibility. Moreover, the proposed biosensor demonstrates superior performance for miR-155 in complex human serum samples and tumor cell lysates, presenting great application potential for early-stage clinical diagnosis.

Circulating miRNA-192 and miR-29a as Disease Progression Biomarkers in Hepatitis C Patients with a Prevalence of HCV Genotype 3.

MicroRNAs miR-29a and miR-192 are involved in inflammatory and fibrotic processes of chronic liver disease, and circulating miR-29a is suggested to diagnose fibrosis progression due to hepatitis C virus (HCV) infection. This study aimed to evaluate the expression profile of circulating miR-192 and 29a in a patient cohort with a high frequency of HCV genotype-3. A total of 222 HCV blood samples were collected and serum were separated. Patients were classified into mild, moderate, and severe liver injury based on their Child-Turcotte-Pugh CTP score. RNA was isolated from the serum and used for quantitative real-time PCR. The HCV genotype-3 (62%) was the predominant HCV genotype. In HCV patients, the serum miR-192 and miR-29a levels were significantly upregulated in comparison to healthy controls (p = 0.0017 and p = 0.0001, respectively). The progression rate of miR-192 and 29a in the patient group with mild was highly upregulated compared to patients with moderate and severe hepatitis infection. The ROC curve of miR-192 and miR-29a of moderate liver disease had a significant diagnostic performance compared to the other HCV-infected groups. The increase in miR-29a and miR-192 serum levels was even slightly higher in patients with HCV genotype-3 than in non-genotype-3 patients. In conclusion, serum miR-192 and miR-29a levels significantly increased during the progression of chronic HCV infection. The marked upregulation in patients with HCV genotype-3 suggests them as potential biomarkers for hepatic disease, independently of the HCV genotype.