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PLASMA MICRORNA-133А LEVEL IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION

Koval S, Snihurska I, Yushko K, Lytvynova O, Berezin A

Georgian Med News, 2019 May.
PMID: 31322515

The aim of research was to investigate the plasma microRNA (miR-133а) level in patients with essential arterial hypertension (EAH). A total of 45 patients with EAH 2-3 degrees aged 52.14 ± 8.25 years and 21 healthy individuals (control group) with comparable age and sex distributions. The following frequency of risk factors was revealed among the examined patients: overweight (53%), dyslipidaemia (73%), pre-diabetes (13%), asymptomatic hyperuricemia (29%); hypertension-mediated organ damage: increased arterial stiffness (27%), left ventricular hypertrophy (55%), atherosclerotic plaque in the carotid artery (40%), microalbuminuria (15%), moderate stage of chronic kidney disease (22%) and cardiovascular diseases: stable ischemic heart disease (11%) and heart failure with preserved ejection fraction of NYHA functional class I (18%). The plasma miR-133a level was determined by polymerase chain reaction using "CFX96 Touch" detection system (BioRad) and "TaqMan microRNA Assay" and "TaqMan® Universal PCR Master Mix" reagents (Thermo Fisher Scientific, USA). It has been established that in patients with EAH the plasma level of miR-133a was significantly lower than in practically healthy individuals (0,182 [0,102; 0,301] ), vs (0,382 [0,198; 0,474]), p <0.05). It has also been revealed a significant decrease in the level of miR-133a in the blood plasma in patients with such organs damage as LVH (0,133 [0,099;0,184]) in comparison with patients without LVH (0,238 [0,155; 0,410]), p <0.05) and also significantly lower than in healthy subjects in the control group (0,382 [0,198; 0,474]), p<0.05). There were no statistically significant differences in the plasma levels of miR-133a in the group of patients with EAH, depending on the presence of risk factors, other organ damage and cardiovascular diseases. The findings suggest the significant role of reducing of plasma levels of miR-133a in the pathogenesis of hypertension itself and in pathological remodeling of the heart.

Matched MeSH terms: MicroRNAs/blood*
MicroRNA-based Biosensors for Early Detection of Cancers

Rezayi M, Farjami Z, Hosseini ZS, Ebrahimi N, Abouzari-Lotf E

Curr Pharm Des, 2018;24(39):4675-4680.
PMID: 30636591 DOI: 10.2174/1381612825666190111144525

Small noncoding microRNAs (miRNAs) are known as noninvasive biomarkers for early detection in various cancers. In fact, miRNAs have key roles in carcinogenicity process such as proliferation, apoptosis and metastasis. After cardiovascular disease, cancer is the second cause of death in the world with an estimated 9.6 million deaths in 2018. So, early diagnosis of cancer is critical for successful treatment. To date, several selective and sensitive laboratory-based methods have been applied for the detection of circulating miRNA, but a simple, short assay time and low-cost method such as a biosensor method as an alternative approach to monitor cancer biomarker is required. In this review, we have highlighted recent advances in biosensors for circulating miRNA detection.

Matched MeSH terms: MicroRNAs/blood*
Fulltext Circulatory microRNA-145 expression is increased in cerebral ischemia

Gan CS, Wang CW, Tan KS

Genet. Mol. Res., 2012;11(1):147-52.
PMID: 22370881 DOI: 10.4238/2012.January.27.1

Cerebral ischemia or ischemic stroke is mainly attributed to vascular and circulation disorders. Among protein biomarkers, RNA profiles have also been identified as markers of ischemic stroke. MicroRNA-145 expression is ostensibly recognized as marker and modulator of vascular smooth muscle cell phenotype; however, expression levels in ischemic stroke had not been investigated. Employing real-time quantitative PCR, we examined the expression profile of circulatory microRNA-145 in healthy control subjects (N = 14) and ischemic stroke patients (N = 32). Circulatory microRNA-145 expression was significantly higher in ischemic stroke patients than in control subjects. This demonstrates that hemostatic mechanisms are affected by ischemic stroke. We conclude that circulating microRNA-145 has potential as a biomarker for ischemic stroke.

Matched MeSH terms: MicroRNAs/blood*
Circulating miR-3197 and miR-2116-5p as novel biomarkers for diabetic retinopathy

Ji H, Yi Q, Chen L, Wong L, Liu Y, Xu G, et al.

Clin Chim Acta, 2020 Feb;501:147-153.
PMID: 31678272 DOI: 10.1016/j.cca.2019.10.036

Diabetic retinopathy (DR) is the leading cause of vision loss among older adults. The goal of this case-control study was to identify circulating miRNAs for the diagnosis of DR. The miRNeasy Serum/Plasma Kit was used to extract serum miRNAs. The μParaflo™ MicroRNA microarray was used to detect the expression levels of the miRNAs. The miRWalk algorithm was applied to predict the target genes of the miRNAs, which were further confirmed by the dual luciferase reporter gene system in HEK293T cells. A microarray was performed between 5 DR cases and 5 age-, sex-, body mass index-, and duration of diabetes-matched type 2 diabetic (T2DM) controls. The quantitative reverse transcription polymerase chain reaction technique was used to validate the differentially expressed circulating miRNAs in 45 DR cases and 45 well-matched controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the circulating miRNAs as diagnostic biomarkers for DR. Our microarray analysis screened out miR-2116-5p and miR-3197 as significantly up-regulated in DR cases compared with the controls. Furthermore, two miRNAs were validated in the 45 DR cases and 45 controls. The ROC analysis suggested that both miR-3197 and miR-2116-5p distinguished DR cases from controls. An additional dual-luciferase reporter gene assay confirmed that notch homolog 2 (NOTCH2) was the target gene of miR-2116-5p. Both miR-3197 and miR-2116-5p were identified as promising diagnostic biomarkers for DR. Future research is still needed to explore the molecular mechanisms of miR-3197 and miR-2116-5p in the pathogenesis of DR.

Matched MeSH terms: MicroRNAs/blood*
Fulltext Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress

Kamalden TA, Macgregor-Das AM, Kannan SM, Dunkerly-Eyring B, Khaliddin N, Xu Z, et al.

Antioxid Redox Signal, 2017 Nov 01;27(13):913-930.
PMID: 28173719 DOI: 10.1089/ars.2016.6844

AIMS: MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.
RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.
INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.

Matched MeSH terms: MicroRNAs/blood*
Fulltext Circulating MicroRNAs in Young Patients with Acute Coronary Syndrome

Tong KL, Mahmood Zuhdi AS, Wan Ahmad WA, Vanhoutte PM, de Magalhaes JP, Mustafa MR, et al.

Int J Mol Sci, 2018 May 15;19(5).
PMID: 29762500 DOI: 10.3390/ijms19051467

Circulating microRNAs (miRNAs) hold great potential as novel diagnostic markers for acute coronary syndrome (ACS). This study sought to identify plasma miRNAs that are differentially expressed in young ACS patients (mean age of 38.5 ± 4.3 years) and evaluate their diagnostic potentials. Small RNA sequencing (sRNA-seq) was used to profile plasma miRNAs. Discriminatory power of the miRNAs was determined using receiver operating characteristic (ROC) analysis. Thirteen up-regulated and 16 down-regulated miRNAs were identified in young ACS patients. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation showed miR-183-5p was significantly up-regulated (8-fold) in ACS patients with non-ST-segment elevated myocardial infarction (NSTEMI) whereas miR-134-5p, miR-15a-5p, and let-7i-5p were significantly down-regulated (5-fold, 7-fold and 3.5-fold, respectively) in patients with ST-segment elevated myocardial infarction (STEMI), compared to the healthy controls. MiR-183-5p had a high discriminatory power to differentiate NSTEMI patients from healthy controls (area under the curve (AUC) of ROC = 0.917). The discriminatory power for STEMI patients was highest with let-7i-5p (AUC = 0.833) followed by miR-134-5p and miR-15a-5p and this further improved (AUC = 0.935) with the three miRNAs combination. Plasma miR-183-5p, miR-134-5p, miR-15a-5p and let-7i-5p are deregulated in STEMI and NSTEMI and could be potentially used to discriminate the two ACS forms.

Matched MeSH terms: MicroRNAs/blood*
Ratiometric Detection of microRNA Using Hybridization Chain Reaction and Fluorogenic Silver Nanoclusters

Wong ZW, Ng JF, New SY

Chem Asian J, 2021 Dec 13;16(24):4081-4086.
PMID: 34668337 DOI: 10.1002/asia.202101145

miRNA (miR)-155 is a potential biomarker for breast cancers. We aimed at developing a nanosensor for miR-155 detection by integrating hybridization chain reaction (HCR) and silver nanoclusters (AgNCs). HCR serves as an enzyme-free and isothermal amplification method, whereas AgNCs provide a built-in fluorogenic detection probe that could simplify the downstream analysis. The two components were integrated by adding a nucleation sequence of AgNCs to the hairpin of HCR. The working principle was based on the influence of microenvironment towards the hosted AgNCs, whereby unfolding of hairpin upon HCR has manipulated the distance between the hosted AgNCs and cytosine-rich toehold region of hairpin. As such, the dominant emission of AgNCs changed from red to yellow in the absence and presence of miR-155, enabling a ratiometric measurement of miR with high sensitivity. The limit of detection (LOD) of our HCR-AgNCs nanosensor is 1.13 fM in buffered solution. We have also tested the assay in diluted serum samples, with comparable LOD of 1.58 fM obtained. This shows the great promise of our HCR-AgNCs nanosensor for clinical application.

Matched MeSH terms: MicroRNAs/blood*
Fulltext Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Duell EJ, Lujan-Barroso L, Sala N, Deitz McElyea S, Overvad K, Tjonneland A, et al.

Int J Cancer, 2017 Sep 01;141(5):905-915.
PMID: 28542740 DOI: 10.1002/ijc.30790

Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p).

Matched MeSH terms: MicroRNAs/blood*
Fulltext Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma

Tan LP, Tan GW, Sivanesan VM, Goh SL, Ng XJ, Lim CS, et al.

Int J Cancer, 2020 04 15;146(8):2336-2347.
PMID: 31469434 DOI: 10.1002/ijc.32656

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein-Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.

Matched MeSH terms: MicroRNAs/blood
Fulltext Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B

Riazalhosseini B, Mohamed R, Apalasamy YD, Langmia IM, Mohamed Z

Rev Soc Bras Med Trop, 2017 Mar-Apr;50(2):161-166.
PMID: 28562750 DOI: 10.1590/0037-8682-0416-2016

INTRODUCTION: Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC.

METHODS:: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB.

RESULTS:: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression.

CONCLUSIONS:: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.

Matched MeSH terms: MicroRNAs/blood*
Fulltext Methods and matrices: approaches to identifying miRNAs for nasopharyngeal carcinoma

Plieskatt JL, Rinaldi G, Feng Y, Levine PH, Easley S, Martinez E, et al.

J Transl Med, 2014;12:3.
PMID: 24393330 DOI: 10.1186/1479-5876-12-3

Nasopharyngeal carcinoma (NPC) is a solid tumor of the head and neck. Multimodal therapy is highly effective when NPC is detected early. However, due to the location of the tumor and the absence of clinical signs, early detection is difficult, making a biomarker for the early detection of NPC a priority. The dysregulation of small non-coding RNAs (miRNAs) during carcinogenesis is the focus of much current biomarker research. Herein, we examine several miRNA discovery methods using two sample matrices to identify circulating miRNAs (c-miRNAs) associated with NPC.

Matched MeSH terms: MicroRNAs/blood

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