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The microRNA (miR)-29 family has been deregulated in several types of hematologic malignancies. However, role of this family and their target genes DNMT3A (DNA methyltransferase 3A) and TET2 (Ten-Eleven Translocation 2) remains unclear. Here, we have made an attempt to determine the relative expression levels of three miRNAs and target genes in patients with newly diagnosed Multiple myeloma (MM) using quantitative real-time PCR. Moreover, the expression levels of selected miRNAs and genes and their correlations with clinical parameters were compared and analyzed. The ROC curve was used to analyze their diagnostic efficacy for MM. The expression level of hsa-miR-29b-3p was significantly higher in patients with newly diagnosed MM compared with the control group. ROC analysis showed that hsa-miR-29b-3p demonstrated a moderate diagnostic power in MM. The relative expression level of hsa-miR-29b-3p in patients with high LDH levels was markedly reduced compared to that in patients with normal and low LDH levels. DNMT3A expression level was significantly increased in patients with high LDH levels and patients with lambda light chain. Our results indicate that hsa-miR-29b-3p may be used as a potential biomarker in the diagnosis of MM. [ABSTRACT FROM AUTHOR]

Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. Methods: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. Results: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene. [ABSTRACT FROM AUTHOR]

Interaction between radiofrequency radiation (RFR) and miRNA which plays paramount role in growth, differentiation, proliferation, and cell death by suppressing one or more target genes, is still unknown. Therefore, the purpose of this study is to investigate the effects of long term 900 MHz mobile phone exposure on some of the miRNA in brain tissues (sham: 7; Exposure : 7)., which were kept in appropriate laboratory conditions for the second phase of our previous study [5]. It is remembered that rats in the exposure group were exposed to 900 MHz RFR for 3 h per day (7 days a week) for one year. For the aim of this study, expression of miRNAs such as rno-miR-22-3p, rnomiR-24-1-3p, rno-miR-132-3p, rno-miR-145-5p, rno-miR-181a-5p, rno-miR-186-5p, rno-miR-195-5p, rno-miR-219a-5p, rno-miR-221-3p and rno-miR-222-3p were investigated. Results indicated that long-term exposure of 900 MHz RF radiation increased only expression of rno-miR-145-5p (adj P * = 0.047) value where 1g average SAR value in brain was 0.198 W/kg. Our results indicated that chronic exposure of 900 MHz RFR has potential to increase expression of rno-miR-145-5p. Therefore, further studies are necessary to understand the relation between 900 MHz mobile phone exposure and diseases related to the expression of rno-miR-145-5p. [ABSTRACT FROM AUTHOR]

Common complex diseases are a result of host and environment interactions. One such putative environmental factor is the electromagnetic field exposure, especially the occupational extremely low frequency (ELF) magnetic field, 50 Hz, 1 mT, whose neurobiological relevance remains elusive. We evaluated the effects of long-term (60 days) ELF-MF exposure on miRNAs previously related to brain and human diseases (miR-26b-5p, miR-9-5p, miR-29a-3p, miR-106b-5p, miR-107, miR-125a-3p). A total of 64 young (3 weeks-old) and mature (10 weeks-old) male/female Wistar-Albino rats were divided into sham and ELF-MF exposed groups. After sacrifice of the animals, blood samples from rat's tail vein and brain tissues were collected. The expression levels of miRNAs were investigated with Real-Time PCR technique and TaqMan probe Technology. All miRNA expression levels of the young female rats show a significant decrease in blood according to brain samples ( p < 0.05), but fewer miRNAs displayed a similar significant decrease in the blood. In conclusion, these new observations might inform future clinical biological psychiatry studies of long-term electromagnetic field exposure, and the ways in which host–environment interactions contribute to brain diseases. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression. Although it is reported in many studies that there are associations between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease and autoimmune disease, the effects of common genetic variants of these genes on male infertility are unclear. To better understand this effect, we performed a case-control study including a total of 108 infertile men with idiopathic azoospermia and 125 fertile control subjects. Real-time polymerase chain reaction was used to genotype six single-nucleotide polymorphisms (SNPs) of microRNA biogenesis pathway genes and the associations between individual and combined genotypes and idiopathic azoospermia were analysed. The results showed significant difference between the individual AA genotype frequency of theGEMIN3(rs197388) gene in the patient and control groups, indicating that the AA genotype may be considered as indicative of a higher predisposition to idiopathic azoospermia. The combined genotype analysis, including six SNPs, revealed statistically significant differences between the patients and control subjects for some combinations. For example, the frequency of genotype distributions of the AA\CA-CC-TT-AT genotype combination for theXPO5-RAN-DICER1-GEMIN3combined loci was significantly different, and it may be considered a predisposition to idiopathic azoospermia. According to the obtained results, both individual and combined genotypes of SNPs from miRNA genes may be used to predict the risk of male infertility with idiopathic azoospermia. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. However, biomarkers that require testing in the brain tissue pose a formidable practical barrier to AD diagnostic innovation. MicroRNAs (miRNAs) are responsible for control of gene expression at the posttranscriptional level and are essential for the function of neuronal networks and neuronal survival. miRNA expression can impact the regulation of APP (amyloid beta A4 precursor protein), PSEN1 (presenilin 1), PSEN2 (presenilin 2), and BACE1 (beta-secretase 1) genes in the brain that were previously implicated in AD pathophysiology. Little is known, however, on the extent to which peripheral tissue (e.g., whole blood) miRNA variation might offer clinical predictive value for AD. Moreover, few studies have examined multiple peripheral miRNA expression data at the same time. We report here, to the best of our knowledge, the first whole-blood-based and parallel study of seven miRNAs ( hsa-miR-9-5p, hsa-miR-29a-3p, hsa-miR-106a-5p, hsa-miR-106b-5p, hsa-miR-107, hsa-miR-125a-3p, and hsa-miR-125b-5p) in relation to AD susceptibility. Notably, these miRNAs are situated 'upstream' to the genes implicated in AD. We measured the whole-blood miRNA expression by a real-time polymerase chain reaction in a large study sample ( n = 281), comprising patients with AD ( n = 172) and healthy controls ( n = 109). A reduction in whole-blood expression of hsa-miR-9-5p, hsa-miR-106a-5p, hsa-miR-106b-5p, and hsa-miR-107 was significantly associated with an increased risk of AD ( p < 0.05). Notably, after receiver operating characteristics curve analyses, hsa-miR-106a-5p displayed, as a predictor variable, 93% specificity and 68% sensitivity. On the other hand, the expression of hsa-miR-29a-3p, hsa-miR-125a-3p, and hsa-miR-125b-5p was not significantly different between patients and controls ( p > 0.05). In conclusion, these observations warrant replication in larger samples while making a contribution to translational research, precision medicine, and biomarker literatures, by expanding the current efforts for AD diagnostic innovation to the realm of epigenomic pathways such as miRNA expression variation among patients. [ABSTRACT FROM AUTHOR]

Aim: Obsessive-compulsive disorder (OCD) is a disorder characterized by the presence of obsessions and/or compulsions. Although disorder etiology and pathogenesis remains unknown, several theories about OCD development have been proposed, and many researchers believe that it is caused by both genetic and environmental factors. In the current study, our aim was to investigate miRNA levels in OCD. Methods: In the current study, we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107, miR125b-5p, and miR155a-5p levels in child and adolescent OCD patients. The research sample consisted of a group of 23 OCD patients and 40 healthy volunteer controls. Results: There was no significant difference in age and sex between the two groups (P>0.05). The levels of miR22-3p, miR24-3p, miR106b-5p, miR125b-5p, and miR155a-5p were significantly increased in the OCD subjects (P≤0.05). There were no statistically significant differences in miR18a-5p or miR107 levels between groups (P≥0.05). Conclusion: There could be a close relationship between levels of circulating miRNAs and OCD. If we could understand how the signaling pathways arranged by miRNAs impact on central nervous system development, function, and pathology, this understanding could improve our knowledge about OCD etiology and treatment. [ABSTRACT FROM AUTHOR]

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Purpose: MicroRNAs (miRNA) play a paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. However, their interaction with radiofrequencies is still unknown. The aim of this study was to investigate the long-term effects of radiofrequency radiation emitted from a Wireless Fidelity (Wi-Fi) system on some of the miRNA in brain tissue. Materials and methods: The study was carried out on 16 Wistar Albino adult male rats by dividing them into two groups such as sham (n = 8) and exposure (n = 8). Rats in the exposure group were exposed to 2.4 GHz radiofrequency (RF) radiation for 24 hours a day for 12 months (one year). The same procedure was applied to the rats in the sham group except the Wi-Fi system was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. miR-9-5p, miR-29a-3p, miR-106b-5p, miR-107, miR-125a-3p in brain were investigated in detail. Results: The results revealed that long-term exposure of 2.4 GHz Wi-Fi radiation can alter expression of some of the miRNAs such as miR-106b-5p (adj p* = 0.010) and miR-107 (adj p* = 0.005). We observed that mir 107 expression is 3.3 times and miR-106b-5p expression is 3.65 times lower in the exposure group than in the control group . However, miR-9-5p, miR-29a-3p and miR-125a-3p levels in brain were not altered. Conclusion: Long-term exposure of 2.4 GHz RF may lead to adverse effects such as neurodegenerative diseases originated from the alteration of some miRNA expression and more studies should be devoted to the effects of RF radiation on miRNA expression levels. [ABSTRACT FROM AUTHOR]

Purpose: We still do not have any information on the interaction between radiofrequency radiation (RF) and miRNA, which play paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. The purpose of this study was to bridge this gap by investigating effects of long-term 900 MHz mobile phone exposure on some of the miRNA in brain tissue. Materials and methods: The study was carried out on 14 Wistar Albino adult male rats by dividing them into two groups: Sham ( n = 7) and exposure ( n = 7). Rats in the exposure group were exposed to 900 MHz RF radiation for 3 h per day (7 days a week) for 12 months (one year). The same procedure was applied to the rats in the sham group except the generator was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. rno-miR-9-5p, rno-miR-29a-3p, rno-miR-106b-5p, rno-miR-107 and rno-miR-125a-3p in brain were investigated in detail. Results: Results revealed that long-term exposure of 900 MHz RF radiation only decreased rno-miR107 (adj P* = 0.045) value where the whole body (rms) SAR value was 0.0369 W/kg. However, our results indicated that other microRNA evaluated in this study was not altered by 900 MHz RF radiation. Conclusion: 900 MHz RF radiation can alter some of the miRNA, which, in turn, may lead to adverse effects. Therefore, further studies should be performed. [ABSTRACT FROM AUTHOR]

Alcohol dependence (AD) is a neuropsychiatric disorder to which both genetic and environmental factors contribute. Especially, multiple genetic factors are promising to explain the etiology of AD. microRNAs (miRNAs) are members of a family of noncoding small RNAs, which are thought to be responsible for the altered gene expression in neuropsychiatric disorders. We hypothesized that single nucleotide polymorphisms (SNPs) in the miRNA biogenesis pathway may result in dysregulation of miRNA levels inside the cell. The aim of this study was to test an association between miRNA biogenesis gene variants and AD risk. Real-time polymerase chain reaction genotyping experiment was conducted on DNA samples from 123 alcohol-dependent patients and 135 healthy controls. We found that AGO1 rs595961 ( χ2=9.066, p=0.003; odds ratio [OR]=0.459, 95% confidence interval [CI]: 0.275-0.768) and AGO2 rs4961280 ( χ2=4.111, p=0.043; OR=0.590, 95% CI: 0.353-0.986) G alleles have significantly altered the risk for AD, and also there is a significant association of GEMIN4 rs910924 ( χ2=5.291, p=0.021; OR=1.913, 95% CI: 1.094-3.344) T allele with the risk for AD. We also found statistically significant difference in AGO1 rs595961 ( χ2=11.139, p=0.001) and DGCR8 rs1640299 ( χ2=13.001, p=0.002) genotype frequencies between case-control groups. This is the first study to investigate the effects of SNPs in the miRNA biogenesis pathway on AD risk. In conclusion, we identified a significant association of miRNA biogenesis genes with altered AD risk, and these results could be a guide to research on the role of miRNAs in AD in the future. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood disorders, although disorders etiology and pathogenesis remains unknown, several theories about ADHD development have been proposed and many researchers believe that it is caused by both genetic and environmental factors. In this study we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107, miR125b-5p and miR155a-5p levels in child and adolescent ADHD patients. The research sample consisted a group of 52 ADHD patients, and 52 healthy volunteer controls. There was no significant difference in age and sex between the two groups ( p > 0.05). miRNA 18a-5p, 22-3p, 24-3p, 106b-5p and 107 levels were statistically significantly decreased in ADHD patients( p < 0.05). miRNA 155a-5p levels were increased in patients group ( p < 0.05). The positive predictive value (PPV) and negative predictive value of miR107 was estimated for the cutoff point of 0.4480. PPV was 70% and NPV was 86.5% for the taken cut off point. There could be a close relationship between levels of circulating miRNAs and ADHD. If we could understand how the signaling pathways arranged by miRNAs, impact on CNS development, function and pathology this can improve our knowledge about ADHD etiology and treatment. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BPD) is a major psychiatric disorder with an unclear pathophysiology. Peripheral blood samples are easily drawn, making them are good candidates for diagnosing diseases. MicroRNAs are small non-coding RNA transcripts that regulate gene expression by binding to the 3'- UTR of mRNAs and directing their degradation. The aim of this study was to use blood plasma to investigate microRNA dysregulations in bipolar manic and euthymic patients.Subjects and Methods: Blood samples were collected from 58 patients with bipolar I disorder (19 manic, 39 euthymic) and 51 healthy controls.Results: Four microRNAs (miR-29a-3p, p = 0.035; miR-106b-5p, p = 0.014; miR-107, p = 0.011; and miR-125a-3p, p = 0.014) were upregulated in the entire bipolar group, compared to the healthy controls. Seven microRNAs (miR-9-5p, p = 0.032; miR-29a-3p, p = 0.001; miR-106a-5p, p = 0.034; miR-106b-5p, p = 0.003; miR-107, p < 0.001; miR-125a-3p, p = 0.016; and miR-125b-5p, p = 0.004) were more upregulated in bipolar manic patients compared to the healthy controls, and two microRNAs (miR-106a-5p, p = 0.013, and miR-107, p = 0.021) showed statistically significant upregulation in the manic patients compared to the euthymic patients.Conclusions: Our results showed greater miRNA dysregulation in the manic patients than in the euthymic patients. Two microRNAs could be more selective for bipolar manic episodes. Future studies should include depressive patients along with euthymic and manic patients. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent complex psychiatric disorders in children as well as adults. ADHD impacts not only the affected individuals but also their families and social and professional networks. The clinical and diagnostic criteria for ADHD remain imprecise, in part, due to lack of robust biomarkers. ADHD comprises multiple subsets of diseases that present a shared set of downstream clinical findings, while displaying extensive molecular heterogeneity. This calls for innovation in diagnostic strategies that can help establish an ADHD diagnosis unequivocally as well as guiding precision medicine in this common mental health disorder. No study has examined, to the best of our knowledge, the upstream regulation of miRNAs that impact the downstream final ADHD phenotype. The latter focus on putative genetic biomarkers that regulate the regulators and can be tested empirically, for example, through genetic association analyses of the biogenesis pathways for miRNAs that impact the ADHD phenotype. Hence, we report here polymorphic variation in 10 miRNA biogenesis pathway candidate genes, including RNASEN, DGCR8, XPO5, RAN, DICER1, TARBP2, AGO1, AGO2, GEMIN3, and GEMIN4, in a large sample from the Eastern Mediterranean region (N= 355; 191 cases and 164 controls). We found that AGO1 rs595961 was significantly associated with ADHD susceptibility ( p < 0.05). While polymorphic variation in other miRNA biogenesis pathway genes did not display a significant association in the present sample, the observations reported herein on miRNA biogenesis variation offer a new avenue of research for innovation in biomarker discovery concerning ADHD and other complex psychiatric diseases with major global health burden. [ABSTRACT FROM AUTHOR]

Objective: Schizophrenia is a devastating psychiatric disorder. Comprehensive research has been performed to identify biomarkers for this disease. Unfortunately we do not yet have a reliable biomarker for schizophrenia. MicroRNAs are 22-nucleotide-long RNA transcripts that regulate expression of genes at post-transcriptional level. To date, a limited number of studies has been done with peripheral tissue of schizophrenia patients. Here we demonstrate microRNA levels in plasma of schizophrenia patients. Methods: Peripheral blood samples were collected from 16 schizophrenia patients and 16 healthy controls. Total RNA was extracted from Peripheral Whole Blood using Tri-Reagent (Sigma). Reverse transcriptase reactions contained 5 μl of extracted total RNA. Quantitative- Comparative CT (ΔΔCT) Real-time PCR was performed in an ABI Prism 7500 Real-Time PCR System (Applied Biosystems) using SDS 2.0.6 software. Results: Schizophrenia patients showed significant upregulation of five microRNAs: miR9-5p (p=0.002), miR29a-3p (p<0.001), miR106b- 5p (p=0.002), miR125a-3p(p<0.001) and miR125b-3p (p=0.018). Conclusion: We found miR106b-5p upregulated in schizophrenia patients. Liu et al. compared 14 healthy controls with 16 depressed patients and found that miR106-5p and four other microRNAs were up regulated in the plasma of depressed patients. Additionally miR106b-5p was found to be downregulated in children with attention deficit / hyperactivity disorder(ADHD). In their unpublished study, Karababa et al. found miR106a-5p and miR106b-5p upregulated in manic patients. Perkins et al. found that miR-9-3p and miR-29a were downregulated and miR-106b was upregulated in the prefrontal cortex of individuals with schizophrenia. We believe combining our results with previous findings increases the likelihood the miR-106 family is disrupted in psychiatric disorders. Limitations of our study are small sample size, cross sectional design, and limited number of microRNA types. Despite these limitations, our study contributes to revealing potential peripheral microRNA signatures and encourages researchers to focus on this field. [ABSTRACT FROM AUTHOR]