miRNAs In Pathogenesis Research Articles

MicroRNAs in fluorosis pathogenesis: impact on dental, skeletal, and soft tissues.

Fluoride-induced toxicity (fluorosis) poses a significant health concern globally, affecting millions of individuals. Understanding the molecular mechanisms underlying fluorosis, particularly the role of microRNAs (miRNAs), is crucial for developing effective preventive and therapeutic strategies. This review explores the pivotal role of miRNAs in the pathogenesis of fluorosis, particularly examining its impact on both hard (skeletal and dental) and soft (brain, liver, kidney, heart, and reproductive organs) tissues. Skeletal fluorosis manifests as abnormal bone mineralization and structure, while dental fluorosis affects enamel formation. In vitro and in vivo studies suggest a significant involvement of miRNAs in the progression of these conditions. For skeletal fluorosis, miR-124, miR-155, and miR-200c-3phave been identified askeyregulators, while miR-296-5p and miR-214-3pare implicatedin dental fluorosis.Moreover, soft tissue fluorosis encompasses a spectrum of adverse effects on various organs, including the brain, liver, kidneys, heart, and reproductive system. In soft tissues, miRNAs, such as miR-124, miR-200c-3p, miR-132, and miR-34b-5p, havebeen linkedto cellular damage and dysfunction. Notably, miRNAs exert their effectsthrough the modulation ofcritical pathways involved in fluorosis pathology, including Wnt signaling, apoptosis, cell cycle, and autophagy. Understanding the regulatory roles of miRNAs in fluorosis pathogenesis holds promise for identifying biomarkers and therapeutic targets. However, further research is needed to elucidate the molecular mechanisms underlying miRNA-mediated responses to fluoride exposure.Integration ofmiRNA research into fluorosis studies could facilitate the development of diagnostic tools and therapeutic interventions, thus mitigating the detrimental effects of fluorosis on both hard and soft tissues.

Role of miRNA in pathogenesis, diagnosis, and prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers and is responsible for the second cancer-related death globally. Many treatment regimens have been developed to cure the disease; however, life expectancy is still low. Therefore, there is an urgent need to explore new selective, specific, and robust diagnosis markers for efficient early recognition of the ailment. Along with the diagnosis, the treatment's effectiveness can be determined by prognostic markers, and miRNAs are excellent tools for the diagnosis and prognosis of HCC. In addition, the altered expression profile of a few miRNAs promotes HCC cell migration and invasion, and selective up- or downregulation of these responsible genes may help mitigate the disorder. On one hand, few of the miRNAs have been found to enhance angiogenesis, a crucial step of tumor growth; on the other hand, upregulation of specific miRNAs is reported to suppress angiogenesis and resulting tumor growth of HCC cells. Exosomal miRNAs have significant implications in promoting angiogenesis, increased endothelial cell permeability, tube formation, and metastasis to hepatic and pulmonary tissues. miRNA also attributes to drug resistance toward chemotherapy and the prevention of autophagy also. Identifying novel miRNA and determining their differential expression in HCC tissue may serve as a potential tool for diagnosis, prognosis, and therapy to enhance the life expectancy and quality of life of HCC patients. In the present review, we have summarized the recent advances in HCC-related research.

Selective miRNA quantitation with high-temperature thermal gel electrophoresis

MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression and correlate to the prognosis of numerous diseases. To support research efforts elucidating the roles of miRNAs in pathogenesis, rapid and inexpensive analytical methods are required to quantify miRNAs from biological samples. The challenge of developing new analyses with these time and cost constraints is compounded by the short sequence lengths and high degrees of homology between miRNAs that hinder detection selectivity. This report describes the development of a high-temperature thermal gel electrophoresis (TGE) method to rapidly quantify miRNAs with single-nucleotide resolution using low-cost microfluidic devices. Fluorescent probes were designed for three miRNAs that differed in sequence by one or two nucleotides. A microfluidic analysis was optimized to enrich miRNA-probe hybrids into a high-concentration band and then automatically initiate a separation to resolve each species. Analyses conducted at 30 °C exhibited significant off-target hybridization, as the different-yet-structurally-similar miRNAs bound to each probe, which biased measurements. To overcome this problem, the stability of thermal gels at elevated temperatures was exploited to conduct analyses. At 50 °C, off-target hybrids melted to prevent their detection without impeding the enrichment or separation of on-target hybrids. Selectivity studies validated that high-temperature TGE prevented off-target hybrids from interfering with the quantitative responses of the target miRNAs. This work demonstrates that TGE affords rapid, highly selective analyses of structurally similar miRNAs in low-complexity microfluidic devices, which is expected to facilitate diverse biomedical research.

Can Echinococcus granulosus-Derived MicroRNAs be Biomarkers for Diagnosis and Follow-up of Cystic Echinococcosis Patients?

Cystic echinococcosis (CE) is a neglected tropical disease caused by the larval stages of Echinococcus granulosus (E. granulosus). MicroRNAs (miRNAs) are small noncoding RNAs acting as mediators in host-parasite interaction. Recently, numerous studies have been conducted on miRNAs in infectious diseases; however, little data are available about the role of miRNAs in pathogenesis and early diagnosis of CE. The current study evaluated the expression of four E. granulosus-derived miRNAs, including egr-miR-125,5p, egr-let-7,5p, egr-miR-2, and egr-miR-71 in fibrotic and healthy liver tissues of 31 CE patients with active and inactive hydatid cysts by qRT-PCR. Of the 31 patients, 48.4% had active cysts (CE1 and CE2), while the remainder had transitional (16.1%) and inactive (35.5%) CE types cysts. The qRT-PCR analysis revealed a significant increase of 11.2, 9.91, 6.2, and 13.1-fold in the fibrotic tissue group for egr-miR-125,5p, egr-let-7,5p, egr-miR-2, and egr-miR-71, respectively. Among these miRNAs, egr-miR-125-5p exhibited the highest area under the curve (AUC) value of 0.8050 for predicting liver fibrosis. Our findings provide new data about the role of E. granulosus-derived miRNAs in pathogenesis of CE. The high AUC of egr-miR125,5p reflecting the possibility of using egr-miR125,5p as biomarker in CE diagnosis. Further studies on serum of CE patients are needed to confirm the potential role of circulating egr-miR-2a-3p and egr-miR-125-5p in the early diagnosis of CE.

Ultrasensitive detection of serum miRNA biomarkers related to papillary thyroid cancer using ligation-initiated phosphorothioated primer-based loop-mediated isothermal amplification

Accurately distinguishing of papillary thyroid cancer (PTC) from benign nodules, at the same time, avoiding overdiagnosis is of great significance. In consideration of the role of miRNA in pathogenesis and progression of tumors, miRNA might also be useful as diagnostic marker for cancer. In this study, a ligation-initiated phosphorothioated primer-based loop-mediated isothermal amplification (PS-LAMP) strategy was established to quantify miRNAs in serum sample, thereby achieving noninvasive diagnosis of PTC. Two linker probes designed from dumbbell-shaped amplicons of LAMP are ligated to obtain an active amplicon only when they are perfectly hybridized with target miRNA, exhibiting high specificity. The introduction of PS modification into inner primers (BIP/FIP) facilitated extra efficient hairpin formation and extension for LAMP, which significantly improved sensitivity. Then, the proposed method was successfully applied in the early diagnosis of PTC, in which circulating serum level of miR-146b-5p and miR-199b-5p could draw a clear distinction between patients and controls. This ligation-initiated PS-LAMP assay opens new avenues for highly sensitive quantification of miRNA biomarkers and thus exhibits a considerable potential utility in clinical diagnosis and prognosis.

MiRNA Expression Profile in Ileocecal Adenocarcinoma Cells Infected with Cryptosporidium

Cryptosporidium spp. is an opportunistic protozoan transmitted by fecal-oral route via oocysts. The agent may cause severe infection especially in individuals with suppressed immune system, due to its intracellular location and ability to cause auto-infection. MicroRNAs (miRNAs) are non-translated endogenous RNA molecules with an average of 22 nucleotides in length that regulate the expression of genes involved in important biological functions such as proliferation, differentiation, apoptosis and immune response. Recent studies have focused on the role of miRNAs in pathogenesis of infectious diseases and their potential to be used as biomarkers. The aim of this study was to determine the miRNA profile of human ileocecal adenocarcinoma (HCT-8) cells at 24 hours of infection with Cryptosporidium spp. In the study, the HCT-8 cell line was infected with Cryptosporidium spp. that were isolated from infected human stool samples and RNA was isolated from the cells 24 hours after infection. After this process, cDNA synthesis was performed and the expression of 95 human miRNA profiles were investigated by polymerase chain reaction (PCR) method. Fold changes of expression were determined by comparison with Cryptosporidium spp. uninfected cell lines. Sequence information of miRNAs and their target genes were performed via TargetScanHuman7.1 and miRDB websites, while gene ontology (GO) pathways of target genes were analyzed with the mirPath v.3 program. It was detected that the expression of 10 miRNAs were upregulated and 11 of them were downregulated compared with the control group. It was observed that, this 21 differentially expressed miRNAs were mainly associated with apoptosis, mitotic cell cycle, and immune response. Hsa-miR-612, hsa-miR-6763-5p, hsa-miR-188-5p, hsa-miR-664b-3p, hsa-miR-210-3p, hsa-let-7e-5p hsa-let-7b-3p, hsa-miR-4787-3p, hsa-miR-548ab, hsa-miR-3714 and hsamiR-4803 were found to be associated with apoptosis; and hsa-miR-612, hsa-miR-664b-3p, hsa-miR210-3p, hsa-let-7e-5p, hsa-let-7b-3p, hsa-miR-548ab, and hsa-miR4803 were found to be associated with mitotic cell cycle. The balance of proliferation and apoptosis is very significant in the development of infection and cancer. It is thought that determination of the effect of miRNAs on proliferation-apoptosis balance could provide information related to the etiopathogenesis and prognosis of infections, and on the role of microorganisms in carcinogenesis. In this study, 12 differentially expressed miRNAs were found to be associated with immune response. This may emphasize the role of miRNAs in the prevention and treatment of infections. It was concluded that, miRNAs could be used in the diagnosis, treatment and prevention of infections with the determination of miRNA's role in the infection mechanism as a result of the increasing number of studies.

Understanding Pharmaco-Epigenomic Response of Antipsychotic Drugs Using Genome-Wide MicroRNA Expression Profile in Liver Cell Line.

Interindividual variability in drug response is a major concern among patients undergoing antipsychotic drug treatment. Apart from genetic and physiological factors, this variability in drug response could also be attributed to epigenetic mechanisms. The microRNAs (miRNAs) are key epigenetic markers that play an important role in pathogenesis and drug response. Several studies have shown that miRNAs are implicated in regulating the expression of various genes involved in drug metabolism and transport. In a conventional clinical setup, it is extremely difficult to distinguish the role of miRNA in pathogenesis and drug response as it is difficult to obtain drug naïve patients. To resolve this issue, we aimed to identify the role of antipsychotic drug treatment in inducing miRNA expression under an in vitro condition using a hepatic cell line. A liver cell line was treated with a maximum tolerable drug dosage model for haloperidol, clozapine in monotherapy, and their combination in polytherapy. Genome-wide miRNA profiling was performed using 60,000 miRNA probes in the microarray format in different treatment groups. Several miRNAs were observed to be differentially expressed impacting the pharmacokinetic, pharmacodynamics, and epigenomics properties of antipsychotic drug treatment. Interestingly, some of these miRNA expression patterns were similar to reported miRNA observations on schizophrenia pathogenesis. This study unravels the potential role of miRNAs in the mechanism of action of the antipsychotic drug and could also reflect in drug-induced side effects. This study also signifies the importance of pharmacoepigenomics approach while evaluating the role of miRNAs in pathogenesis.

Diverse Roles and Targets of miRNA in the Pathogenesis of Testicular Germ Cell Tumour.

Simple SummaryTesticular germ cell tumour (TGCT) is the most common malignancy among young males in many parts of the world. Although it is highly remediable, treatments lead to long-term comorbidities, and therefore, it warrants a better prognosis. The presence of several risk loci in non-coding regions supports a functional role of miRNAs in TGCT development, and recent studies point to the emerging roles of miRNA and the complexity of miRNA-mediated gene regulation in TGCTs. miRNAs may act as oncogenes or tumour suppressors in TGCT by regulating targets involved in cell proliferation, apoptosis, and metastasis. Here, we summarise the gene regulation and function of miRNAs involved in TGCT pathogenesis.Testicular germ cell tumour (TGCT) is the most common cancer type among young adults in many parts of the world. Although the pathogenesis of TGCT is not well understood, the involvement of heritable components is evident, and the risk is polygenic. Genome-wide association studies have so far found 78 susceptibility loci for TGCT, and many of the loci are in non-coding regions indicating the involvement of non-coding RNAs in TGCT pathogenesis. MicroRNAs (miRNAs), a class of non-coding RNAs, have emerged as important gene regulators at the post-transcriptional level. They are crucial in controlling many cellular processes, such as proliferation, differentiation, and apoptosis, and an aberrant miRNA expression may contribute to the pathogenesis of several cancers, including TGCT. In support of this notion, several studies reported differential expression of miRNAs in TGCTs. We previously demonstrated that miRNAs were the most common group of small non-coding RNAs in TGCTs, and several functional studies of miRNAs in TGCTs suggest that they may act as either oncogene or tumour suppressors. Moreover, individual miRNA targets and downstream pathways in the context of TGCT development have been explored. In this review, we will focus on the diverse roles and targets of miRNAs in TGCT pathogenesis.

Understanding the role of miRNAs in the pathogenesis of brain arteriovenous malformations

Brain arteriovenous malformations (AVMs) are abnormal vessels that are prone to rupture, causing life-threatening intracerebral hemorrhage (ICH). Understanding the molecular basis of pathogenesis, timely diagnosis, and treatment of brain AVMs are some of the urgent problems in neurosurgery. MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene-expression posttranscriptionally. MiRNAs are involved in almost all biological processes, including cell proliferation, apoptosis, and cell differentiation. Recent studies have shown that miRNAs can be involved in brain AVMs formation and rupture. There are also extracellular forms of miRNAs. Circulating miRNAs have been detected in the blood circulation and other body fluids. Owing to their stability and resistance to endogenous RNase activity, circulating miRNAs have been proposed as diagnostic and prognostic biomarkers for various diseases, such as tumors, cardiovascular and autoimmune diseases. In this review, we summarized the role of some miRNAs in brain AVMs pathogenesis and discussed their potential clinical application as non-invasive biomarkers.

Altered microRNAs in C3H10T1/2 cells induced by p.E95K mutant IHH signaling

BackgroundIndian Hedgehog (IHH), an important cell signaling protein, plays a key regulatory role in development of cartilage and chondrogenesis. Earlier studies have shown that heterozygous missense mutations in IHH gene may cause brachydactyly type A1 (BDA1), an autosomal dominant inheritance disease characterized by apparent shortness or absence of the middle phalanges of all digits. MicroRNAs (miRNAs) have been found to be significant post-transcriptional regulators of gene expression and significantly influence the process of bone-development. Therefore, it is possible that miRNAs are involved in the mechanism underlying the development of BDA1. However, the relationship between miRNAs and the pathogenesis of BDA1 remains unclear.MethodsIn this study, we used microarray-based miRNA profiling to investigate the role of miRNAs in BDA1 by characterization of differentially expressed miRNAs in C3H10T1/2 cell line induced by wild type (WT) and p.E95K mutant (MT) IHH signaling.ResultsOur results identified 6 differentially expressed miRNAs between WT and control (CT) group and 5 differentially expressed miRNAs between MT and CT groups. In particular, miR-135a-1-3p was found to be a significantly differentially expressed miRNA between WT and CT group. Results of dual-luciferase reporter gene experiment successfully discovered Hoxd10 was one of the target gene of miR-135a-1-3p. Additionally, our pathway analysis revealed that the targets of these miRNAs of interest were highly involved with Runx1/2, Notch and collagen-related pathways.ConclusionsTaken together, our findings provided important clue for future study of the process of miRNA-regulation in IHH signaling and novel insights into the regulatory role of miRNA in pathogenesis of BDA1.

Diagnostic and therapeutic potential of exosomal miRNAs in Alzheimer's disease.

Diagnostic and therapeutic potential of exosomal miRNAs in Alzheimer's disease.

Circulating exosomal miRNAs in cardiovascular disease pathogenesis: New emerging hopes.

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality. Standard therapies have failed to significantly increase patients' survival. Moreover, the majority of conventional screening procedures are ineffective for the diagnosis of CVDs at early stages. Accumulating evidence suggests that numerous cell types release a class of nano-sized vesicles named exosomes into the extracellular space. Exosomes are widely distributed in various body fluids and contain a number of diverse biomolecules such as proteins, lipids, and both mRNA and noncoding RNAs which reflect host-cell molecular architecture. MicroRNAs (miRNAs), which can be found in exosomes, could be taken up by both neighboring and distal cells. Not only has recent evidence indicated the regulatory role of exosomal miRNAs in the pathogenesis of CVD, but it has also been shown that differential expression of exosomal miRNAs in CVDs has made them promising biomarkers for early detection of CVDs. Owing to these remarkable features, exosomal miRNAs have emerged as hot spots in research. This review summarizes the role of exosomal miRNAs in the pathogenesis of CVDs and discusses their potential application in the clinical setting as both therapeutic and diagnostic tools.

Meta-analyses identify differentially expressed micrornas in Parkinson's disease.

MicroRNA (miRNA)-mediated (dys)regulation of gene expression has been implicated in Parkinson's disease (PD), although results of miRNA expression studies remain inconclusive. We aimed to identify miRNAs that show consistent differential expression across all published expression studies in PD. We performed a systematic literature search on miRNA expression studies in PD and extracted data from eligible publications. After stratification for brain, blood, and cerebrospinal fluid (CSF)-derived specimen, we performed meta-analyses across miRNAs assessed in three or more independent data sets. Meta-analyses were performed using effect-size- and p-value-based methods, as applicable. After screening 599 publications, we identified 47 data sets eligible for meta-analysis. On these, we performed 160 meta-analyses on miRNAs quantified in brain (n = 125), blood (n = 31), or CSF (n = 4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted α = 3.13 × 10-4 ) differentially expressed miRNAs in brain (n = 3) and blood (n = 10) with consistent effect directions across studies. The most compelling findings were with hsa-miR-132-3p (p = 6.37 × 10-5 ), hsa-miR-497-5p (p = 1.35 × 10-4 ), and hsa-miR-133b (p = 1.90 × 10-4 ) in brain and with hsa-miR-221-3p (p = 4.49 × 10-35 ), hsa-miR-214-3p (p = 2.00 × 10-34 ), and hsa-miR-29c-3p (p = 3.00 × 10-12 ) in blood. No significant signals were found in CSF. Analyses of genome-wide association study data for target genes of brain miRNAs showed significant association (α = 9.40 × 10-5 ) of genetic variants in nine loci. We identified several miRNAs that showed highly significant differential expression in PD. Future studies may assess the possible role of the identified brain miRNAs in pathogenesis and disease progression as well as the potential of the top blood miRNAs as biomarkers for diagnosis, progression, or prediction of PD. ANN NEUROL 2019;85:835-851.

Urinary miRNA-29a-3p levels are associated with metabolic parameters via regulation of IGF1 in patients with metabolic syndrome.

Circulating microRNAs (miRNAs or miRs) have been demonstrated to serve as diagnostic and prognostic biomarkers in metabolic syndrome (MetS). The role of urinary miRNAs in MetS diagnosis remains unknown. Here, elevated miR-29a-3p levels were observed in urine samples of patients with MetS compared with control subjects using a microarray analysis (n=4/group) and validation via reverse transcription-quantitative polymerase chain reaction (n=40/group). Associations between urinary miR-29a-3p levels and parameters associated with metabolism, such as adiposity, insulin resistance, lipid profiles and hepatic enzymes were further assessed. Multiple linear regression analyses revealed that urinary miR-29a-3p levels were independently correlated with fasting insulin (β=0.561; P<0.001), high density lipoprotein-cholesterol (β=0.242; P<0.001) and body mass index (β=-0.141; P<0.05). The area under the receiver operating characteristic curve was 0.776 and miR-29a-3p had a diagnostic value for MetS with 68.2% sensitivity and 77.3% specificity. Furthermore, insulin-like growth factor 1 was identified as a target of miR-29a-3p by searching bioinformatics databases and was validated by dual-luciferase reporter and western blot assays. In conclusion, elevated urinary miR-29a-3p levels were positively associated with MetS and demonstrated to have a potential value as biomarkers in the diagnosis of MetS. The findings provided a better understanding of the role of urinary miRNAs in pathogenesis of MetS.

Recent research progress of microRNAs in hypertension pathogenesis, with a focus on the roles of miRNAs in pulmonary arterial hypertension.

Hypertension is the most widespread disease in the world affecting humans and imparts a significant cardiovascular and renal risk to patients, and extensive research over the past few decades has enhanced our understanding of the underlying pathogenesis of hypertension. A growing number of studies have shown that miRNAs are involved in the pathological mechanisms of hypertension. This review summarizes the current understanding of miRNA-mediated modulation of gene expression in the hypertension pathogenesis in the past few years. A systematic review of PUBMED, EMBASE and SCOPUS was conducted for studies published in the past few years. The review covers three topics: miRNAs in pulmonary arterial hypertension (PAH), miRNAs and systemic arterial hypertension (SAH), miRNAs and application in hypertension. This review summarizes the current understanding of miRNA-mediated modulation in the hypertension pathogenesis in the past few years, with especially emphasis on miRNAs in PAH. We also discussed the roles of miRNAs in SAH, and the therapeutic applications of these miRNAs will be detailed discussed in this review. Evidence suggests that miRNAs are involved in the pathological mechanisms of hypertension, and the roles of miRNAs in the hypertension pathogenesis are confirmed. We need to further investigate the regulated roles of miRNAs in the pathogenesis of hypertension and the application of miRNAs in the diagnosis and treatment of this disease in the future.

Application and progress of miRNA in chronic rhinosinusitis

Chronic rhinosinusitis(CRS) is one of upper respiratory inflammatory diseases, with a high incidence. It affects the patient's work efficiency and quality of life seriously. However, the pathogenesis of disease is not definite. In recent years, some reports have proved miRNA play an important role in the development and occurrence of CRS. This paper reviewed the role of miRNA in pathogenesis,diagnosis and treatment of chronic rhinosinusitis.

Identification of a Specific miRNA Profile in HIV-Exposed Seronegative Individuals.

MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression that play important roles in viral infections. Alterations of specific miRNAs are described in HIV infection, suggesting a role for miRNAs in pathogenesis of this disease. We verified whether a particular miRNA signature could be identified in natural resistance to HIV-1. Expression level of 84 miRNAs was analyzed by RT-qPCR in plasma and unstimulated peripheral blood mononuclear cell (PBMC) of 30 seronegative individuals repeatedly exposed to HIV-1 (HESN), 30 HIV seropositive subjects (HIV+), and 30 healthy controls (HC). Results were confirmed by individual RT-qPCR in in vitro HIV-1-infected PBMC and in their cell culture medium. Dicer and Drosha expression was analyzed in basal PBMC. Whereas Dicer and Drosha expression was comparable in HESN, HIV+ and HC, several miRNAs were upregulated both in HESN and HIV+ compared with HC. Furthermore, miRNA-29a and miR-223 were upregulated in both unstimulated PBMC and plasma of HESN alone; their expression was reduced upon in vitro HIV-1 infection of HESN PBMC indicating that, upon infection, they are secreted in the extracellular milieu. These results were confirmed by individual qPCR. Our studies demonstrate that HIV-1 exposure modifies miRNAs expression even in the absence of productive infection. Because those miRNAs that are specifically increased only in HESN have been known to reduce HIV-1 replication, their modulation could represent an important mechanism in resistance to HIV-1 infection.

Genome technologies in pulmonology: a role of microRNA in asthma and COPD development

MicroRNAs (miRNAs) are small noncoding RNA molecules that affect gene expression and thus take part in the epigenetic regulation of almost all physiological and pathological processes. About 1,800 human miRNAs have been discovered to date; however, biological functions and protein targets for the majority remain to be unknown. Within the respiratory system, miRNAs contribute to the lung growth and lifelong maintenance of pulmonary homeostasis. Recently, the leading role of miRNAs in pathogenesis of various pulmonary diseases has been found, including asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Due to a significant progress in studying interactions between genes and their products and environmental factors, a great role of epigenetic variability, which is gene expression change not related to DNA damage, but could be inherited consistently, became apparent. There are three levels of epigenetic regulation corresponding to three main mechanisms: genomic (DNA methylation), proteomic (histone modification) and transcriptomic (regulation through RNA, primarily miRNA). Extending our knowledge on a role of miRNAs for the respiratory system could open new therapeutic targets and diagnostic markers for respiratory diseases, particularly asthma and COPD.

Stress response factors as hub-regulators of microRNA biogenesis: implication to the diseased heart.

MicroRNAs (miRNAs) are important regulators of heart function and then an intriguing therapeutic target for plenty of diseases. The problem raised is that many data in this area are contradictory, thus limiting the use of miRNA-based therapy. The goal of this review is to describe the hub-mechanisms regulating the biogenesis and function of miRNAs, which could help in clarifying some contradictions in the miRNA world. With this scope, we analyse an array of factors, including several known agents of stress response, mediators of epigenetic changes, regulators of alternative splicing, RNA editing, protein synthesis and folding and proteolytic systems. All these factors are important in cardiovascular function and most of them regulate miRNA biogenesis, but their influence on miRNAs was shown for non-cardiac cells or some specific cardiac pathologies. Finally, we consider that studying the stress response factors, which are upstream regulators of miRNA biogenesis, in the diseased heart could help in (1) explaining some contradictions concerning miRNAs in heart pathology, (2) making the role of miRNAs in pathogenesis of cardiovascular disease more clear, and therefore, (3) getting powerful targets for its molecular therapy.

Identification of microRNAs from Atlantic salmon macrophages upon Aeromonas salmonicida infection

Computational approach was used in to identify potent macrophage specific miRNAs involved in basic biological process of Salmo salar. Analysis of 1119 ESTs from macrophages of Atlantic salmon (Salmo salar) infected with Aeromonas salmonicida revealed expression of 3 miRNAs. Phylogenetic analysis of both the pre-miRNA sequence revealed its evolutionarily conserved nature among various species. Identified targets of the predicted miRNAs revealed the role of miRNA in pathogenesis, stress response and allosteric exchange of histones. Further detailed studies of these miRNAs will help in revealing its function in different biological process necessary for the action of macrophages upon pathogen infection.