Important Role Of miRNAs Research Articles

CMC: Cancer miRNA Census - a list of cancer-related miRNA genes.

A growing body of evidence indicates an important role of miRNAs in cancer; however, there is no definitive, convenient-to-use list of cancer-related miRNAs or miRNA genes that may serve as a reference for analyses of miRNAs in cancer. To this end, we created a list of 165 cancer-related miRNA genes called the Cancer miRNA Census (CMC). The list is based on a score, built on various types of functional and genetic evidence for the role of particular miRNAs in cancer, e.g. miRNA-cancer associations reported in databases, associations of miRNAs with cancer hallmarks, or signals of positive selection of genetic alterations in cancer. The presence of well-recognized cancer-related miRNA genes, such as MIR21, MIR155, MIR15A, MIR17or MIRLET7s, at the top of the CMC ranking directly confirms the accuracy and robustness of the list. Additionally, to verify and indicate the reliability of CMC, we performed a validation of criteria used to build CMC, comparison of CMC with various cancer data (publications and databases), and enrichment analyses of biological pathways and processes such as Gene Ontology or DisGeNET. All validation steps showed a strong association of CMC with cancer/cancer-related processes confirming its usefulness as a reference list of miRNA genes associated with cancer.

The Bone Microenvironment Soil in Prostate Cancer Metastasis: An miRNA Approach.

Bone metastatic prostate cancer (PCa) is associated with a high risk of mortality. Changes in the expression pattern of miRNAs seem to be related to early aspects of prostate cancer, as well as its establishment and proliferation, including the necessary steps for metastasis. Here we compiled, for the first time, the important roles of miRNAs in the development, diagnosis, and treatment of bone metastasis, focusing on recent in vivo and in vitro studies. PCa exosomes are proven to promote metastasis-related events, such as osteoblast and osteoclast differentiation and proliferation. Aberrant miRNA expression in PCa may induce abnormal bone remodeling and support tumor development. Furthermore, miRNAs are capable of binding to multiple mRNA targets, a dynamic property that can be harnessed for the development of treatment tools, such as antagomiRs and miRNA mimics, which have emerged as promising candidates in PCa treatment. Finally, miRNAs may serve as noninvasive biomarkers, as they can be detected in tissue and bodily fluids, are highly stable, and show differential expression between nonmetastatic PCa and bone metastatic samples. Taken together, the findings underscore the importance of miRNA expression profiles and miRNA-based tools as rational technologies to increase the quality of life and longevity of patients.

MicroRNAs and Microcystins Induce Immune Disorders

Background: Cyanobacterial blooms caused by eutrophication can not only worsen the water environment, but also produce cyanobacterial toxins when some toxic cyanobacterial blooms proliferate. Microcystin is one of the most abundant cyanobacterial toxins found in reservoirs worldwide. Among its isomer, microcystin-leucine-arginine (MC-LR) is the most abundant and most toxic variety. Various experiments have clearly shown that MC-LR has hepatotoxicity and carcinogenicity, but there are relatively few studies on its immune damage effect. Numerous studies have shown that microRNAs (miRNAs) are involved in a wide range of biological processes. Do miRNAs also play a role in immune disorders caused by microcystin exposure? This is the question to be discussed in this study. Objective: By reviewing the effects of microcystins on the immune system, the changes of miRNAs caused by microcystins exposure and the role of miRNAs in immune regulation, we further explore the possible important role of miRNAs in immune disorders induced by microcystins exposure. Methods: Firstly, evidence of the influence of microcystin on immune system was collected, then the influence of microcystin exposure on microRNAs expression was reviewed, and finally, the role of microRNAs in immune regulation was explored. Conclusions: Exposure to microcystin in vitro or in vivo can cause changes in the expression of miRNAs, as well as corresponding responses from the body's immune system. There has been evidence that miRNAs are involved in a variety of immune regulatory processes in the body, but there are still relatively few studies on the role of miRNAs in immune disorders caused by microcystins exposure.

MicroRNAs in the Regulation of Solute Carrier Proteins Behind Xenobiotic and Nutrient Transport in Cells.

Altered metabolism, such as aerobic glycolysis or the Warburg effect, has been recognized as characteristics of tumor cells for almost a century. Since then, there is accumulating evidence to demonstrate the metabolic reprogramming of tumor cells, addiction to excessive uptake and metabolism of key nutrients, to support rapid proliferation and invasion under tumor microenvironment. The solute carrier (SLC) superfamily transporters are responsible for influx or efflux of a wide variety of xenobiotic and metabolites that are needed for the cells to function, as well as some medications. To meet the increased demand for nutrients and energy, SLC transporters are frequently dysregulated in cancer cells. The SLCs responsible for the transport of key nutrients for cancer metabolism and energetics, such as glucose and amino acids, are of particular interest for their roles in tumor progression and metastasis. Meanwhile, rewired metabolism is accompanied by the dysregulation of microRNAs (miRNAs or miRs) that are small, noncoding RNAs governing posttranscriptional gene regulation. Studies have shown that many miRNAs directly regulate the expression of specific SLC transporters in normal or diseased cells. Changes of SLC transporter expression and function can subsequently alter the uptake of nutrients or therapeutics. Given the important role for miRNAs in regulating disease progression, there is growing interest in developing miRNA-based therapies, beyond serving as potential diagnostic or prognostic biomarkers. In this article, we discuss how miRNAs regulate the expression of SLC transporters and highlight potential influence on the supply of essential nutrients for cell metabolism and drug exposure toward desired efficacy.

Impacts of MicroRNAs Induced by the Gut Microbiome on Regulating the Development of Colorectal Cancer.

Although a dysfunctional gut microbiome is strongly linked to colorectal cancer (CRC), our knowledge of the mediators between CRC and the microbiome is limited. MicroRNAs (miRNAs) affect critical cellular processes, such as apoptosis, proliferation, and differentiation, and contribute to the regulation of CRC progression. Increasingly, studies found that miRNAs can significantly mediate bidirectional interactions between the host and the microbiome. Notably, miRNA expression is regulated by the gut microbiome, which subsequently affects the host transcriptome, thereby influencing the development of CRC. This study typically focuses on the specific functions of the microbiome in CRC and their effect on CRC-related miRNA production and reviews the role of several bacteria on miRNA, including Fusobacterium nucleatum, Escherichia coli, enterotoxigenic Bacteroides fragilis, and Faecalibacterium prausnitzii. Based on the important roles of miRNAs and the gut microbiome in CRC, strategies for modulating miRNA expression and regulating the gut microbiome composition need to be applied, such as bioactive dietary components and fecal microorganism transplantation.

Regulatory role of miRNAs in Wnt signaling pathway linked with cardiovascular diseases

MicroRNAs (miRNAs) are discovered in science about 23 years ago. These are short, a series of non-coding, single-stranded and evolutionary conserved RNA molecules found in eukaryotic cells. It involved post-transcriptional fine-tune protein expression and repressing the target of mRNA in different biological processes. These miRNAs binds with the 3′-UTR region of specific mRNAs to phosphorylate the mRNA degradation and inhibit the translation process in various tissues. Therefore, aberrant expression in miRNAs induces numerous cardiovascular diseases and developmental defects. Subsequently, the miRNAs and Wnt singling pathway are regulating a cellular process in cardiac development and regeneration, maintain the homeostasis and associated heart diseases. In Wnt signaling pathway majority of the signaling components are expressed and regulated by miRNAs, whereas the inhibition or dysfunction of the Wnt signaling pathway induces cardiovascular diseases. Moreover, inadequate studies about the important role of miRNAs in heart development and diseases through Wnt signaling pathway has been exist still now. For this reason in present review we summarize and update the involvement of miRNAs and the role of Wnt signaling in cardiovascular diseases. We have discussed the mechanism of miRNA functions which regulates the Wnt components in cellular signaling pathway. The fundamental understanding of Wnt signaling regulation and mechanisms of miRNAs is quite essential for study of heart development and related diseases. This approach definitely enlighten the future research to provide a new strategy for formulation of novel therapeutic approaches against cardiovascular diseases.

MicroRNA let-7a, -7e and -133a attenuate hypoxia-induced atrial fibrosis via targeting collagen expression and the JNK pathway in HL1 cardiomyocytes

Abstract Background Atrial fibrillation (AF) is becoming an enormous public health challenge, and it is associated with major cardiovascular morbidity and mortality. There is a need for a better understanding of the causes and consequences of the hypoxia-related development of AF and atrial remodeling. Fibrosis is a hallmark of atrial structural remodeling. Micro-ribonucleic acids (miRNAs) have been reported to have an impact on the pathogenesis of cardiac diseases. Evidence that specific miRNAs can influence AF related to atrial structural remodeling and fibrosis via the modulation of collagens under myocardial hypoxic conditions is lacking. The aim of this study was to investigate the role of miRNAs in the modulation of fibrotic molecular mechanisms in response to hypoxic conditions, which may mediate atrial fibrosis. Methods Hypoxia was induced by cobalt chloride and hypoxia chamber respectively. MiRNA arrays were used to identify the specific miRNAs associated with the modulation of fibrotic genes. Luciferase assay, real-time polymerase chain reaction, immunofluorescence and Western blotting were used to investigate the effects of miRNAs on the expressions of the fibrotic markers collagen I and III (COL1A, COL3A) and phosphorylation levels of the stress kinase c-Jun N-terminal kinase (JNK) pathway in cultured HL-1 atrial cardiomyocytes cell line. Results COL1A and COL3A were found to be the direct regulatory targets of miR-let-7a, miR-let-7e and miR-133a in hypoxic atrial cardiac cells in vitro. The expressions of COL1A and COL3A were influenced by treatment with miRNA mimic and antagomir. The delivery of miR-133a, miR-let-7a or miR-let-7e inhibited hypoxia-induced collagen expression. The JNK pathway was critical in the pathogenesis of atrial fibrosis. Inhibition of JNK phosphorylation (JNK inhibitor SP600125) could be able to increase expression of miRNAs and repressed the fibrotic markers COL1A and COL3A which in turn might reduce the arrhythmogenic atrial remodeling. This study highlights the important role of miRNA in hypoxia-related atrial remodeling as well as atrial fibrosis. Conclusion MiRNA let-7a, miR-let-7e and miR-133a play important roles in hypoxia-related atrial fibrosis by inhibiting collagen expression and post-transcriptional repression by the JNK pathway. These novel findings may lead to the development of new therapeutic strategies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the grants from the Ministry of Science and Technology (MOST), Taiwan, ROC Regulation of cardiac fibrosisRegulation of collagen types by miRNAs

Hepatic microRNAs in Type II Diabetes Pathogenesis

Background/Objective: 
 Diabetes mellitus is a disease with increasing incidence worldwide affecting more than 435 million patients, most of whom have Type II diabetes (T2D). Of the many organs affected by T2D, the liver is responsible for much of the dysregulated metabolic pathways in response to insulin signaling. These include, but are not limited to gluconeogenesis, glycogen storage, fatty acid and cholesterol biosynthesis and transport, and fatty acid oxidation. Recent studies show significant differences in miRNA expression profiles between healthy and disease states of T2D. This implicates an important role of miRNAs in T2D pathogenesis and makes miRNAs an attractive therapeutic target and diagnostic marker for T2D patients. The aim of this review is to provide an overview of the hepatic miRNAs relevant to T2D pathogenesis. 
 
 Methods: 
 We compiled and reviewed articles from the PubMed database that were relevant to miRNAs and T2D pathogenesis in the liver. 
 
 Results: 
 We found that hepatic miRNAs affect most if not all dysregulated metabolic pathways in T2D pathogenesis, which we categorized into carbohydrate metabolism, lipid metabolism, and insulin signaling. The miRNAs that are most represented in our literature include miR-122, miR-33a/b, miR-29, and miR-21. These miRNAs target a variety of molecules, including transcription factors that are master regulators of metabolic pathways (FOXO1, HNF4α), lipid transporters (ABCA1, ABCG1), or key insulin signaling molecules (IRS1/2, caveolin-1). In addition, circulating miR-122 is associated with the risk of developing metabolic syndrome and T2D in the general population. 
 
 Conclusion and Potential Impact: 
 Multiple miRNAs are dysregulated in the liver of animal models of T2D. Administration of miRNA mimics or antagomirs to correct aberrant miRNA expression improved the pathophysiology in vivo. miRNAs are also promising tools as markers for disease development. Ultimately, the identification of miRNAs can guide future research to facilitate the diagnosis and improve the treatment of T2D.

Antitumour Activity of the Ribonuclease Binase from Bacillus pumilus in the RLS40 Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning

The important role of miRNA in cell proliferation and differentiation has raised interest in exogenous ribonucleases (RNases) as tools to control tumour-associated intracellular and extracellular miRNAs. In this work, we evaluated the effects of the RNase binase from Bacillus pumilus on small non-coding regulatory RNAs in the context of mouse RLS40 lymphosarcoma inhibition. In vitro binase exhibited cytotoxicity towards RLS40 cells via apoptosis induction through caspase-3/caspase-7 activation and decreased the levels of miR-21a, let-7g, miR-31 and miR-155. Intraperitoneal injections of binase in RLS40-bearing mice resulted in the retardation of primary tumour growth by up to 60% and inhibition of metastasis in the liver by up to 86%, with a decrease in reactive inflammatory infiltration and mitosis in tumour tissue. In the blood serum of binase-treated mice, decreases in the levels of most studied miRNAs were observed, excluding let-7g, while in tumour tissue, the levels of oncomirs miR-21, miR-10b, miR-31 and miR-155, and the oncosuppressor let-7g, were upregulated. Analysis of binase-susceptible miRNAs and their regulatory networks showed that the main modulated events were transcription and translation control, the cell cycle, cell proliferation, adhesion and invasion, apoptosis and autophagy, as well as some other tumour-related cascades, with an impact on the observed antitumour effects.

MiR-448 targets BLC2 and inhibits the growth of pituitary adenoma cells.

There is an increasing body of evidence indicating the important roles of miRNAs in the progression of pituitary adenoma. Recent studies have shown decreased expression and tumor suppressive function of miR-448 in cancers; however, the clinical significance of miR-448 in pituitary adenoma has remained largely unknown. In our study, we found that miR-448 was down-regulated in pituitary adenoma tissues and cell lines. Overexpression of miR-448 significantly inhibited the proliferation and migration of pituitary adenoma cells. Increased cell apoptosis was also observed with overexpression of miR-448. To further understand the mechanisms behind the regulation of pituitary adenoma by miR-448 in, the targets of miR-448 were predicted using the bioinformatics tools. B cell lymphoma 2 (BCL2) was identified as a target of miR-448. MiR-448 bound the 3'-untranslated region (UTR) of BCL2 and inhibited the expression of BCL2 in pituitary adenoma cells. There was a consistent and significantly negative correlation between the level of miR-448 and BCL2 in pituitary adenoma tissues. When BCL2 was highly expressed, the inhibitory impact of miR-448 on the proliferation and apoptosis of pituitary adenoma cells was significantly inhibited. Collectively, our findings emphasize the significance of the miR-448-BCL2 axis in the development of pituitary adenoma, highlighting the potential therapeutic significance of miR-448 in pituitary adenoma.

Abstract A02: The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma

Abstract Emerging pieces of evidence have proved an important role of miRNAs in tumorigenesis and progression. However, the function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. Quantitative reverse transcription-polymerase chain was used to detect the expression level of miR-449b-3p in NPC cell lines and tissues. We performed cell viability assay, colony formation, flow cytometric, transwell assay, and wound-healing assay to assess the ability of cell proliferation, apoptosis, invasion, and migration in vitro, respectively. NPC xenograft tumor and lymph node metastatic mice model were conducted to validate the function of miR-449b-3p in vivo. Luciferase reporter assay, ChIP assay, and Western blot analysis were actualized to explore the mechanism underlying the miR-449b-3p on NPC metastasis. Here we showed that miR-449b-3p was downregulated in NPC specimens (p<0.001) and cells (p<0.05), and most of the patients with advanced-stage NPC had an impaired expression of miR-449b-3p, on the contrary, early-stage NPC patients had a high level of miR-449b-3p (p<0.001). Moreover, miR-449b-3p inhibited NPC metastasis both in vitro and in vivo. Further investigation revealed that a disintegrin and metalloproteinase 17 (ADAM17) was the direct target of miR-449b-3p. Rescue experiments suggested that the downregulation of ADAM17 in miR-449b-3p inhibited cells partially reversed the inhibition of cell invasion and migration. We also found that ADAM17 could conversely suppress the promoter activity and expression of miR-449b-3p via inducing NF-κB transcriptional activity. In conclusion, our study provides new insights into the mechanism underlying the invasion and metastasis in NPC. The novel miR-449b-3p/ADAM17/NF-κB feedback loop in NPC could potentially be a target for clinical treatment in NPC. Citation Format: Qian Fei, Ming-Yu Du, Ning Jiang, Li Yin, Xia He. The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A02.

CHARACTERISTICS OF miRNA INTERACTION WITH mRNA GENES OF T. AESTIVUM C2H2, ERF, GRAS TRANSCRIPTION FACTORS FAMILIES

The molecular mechanisms for increasing plant productivity remain poorly understood. Genes of C2H2, GRAS, ERF transcription factors (TFs) families play a key role in the physiological processes of plants, including wheat. In recent years, the important role of miRNAs in the regulation of the expression of many genes involved in the formation of productivity has been established. Wheat miRNA (mRNA-inhibiting RNA) target genes are involved in the regulation of the development of flowers, seeds, root, shoots, and responses to abiotic and biotic stresses. The miRNAs binding sites in mRNAs of C2H2, ERF, GRAS TFs families were performed using the MirTarget program, which calculates the free energy of miRNA binding with mRNA, the schemes and positions of nucleotide interactions with binding sites. Wheat genes were used as the object of the study, since wheat is one of the main grain crops in Kazakhstan and in many other countries. The presence of miRNA binding sites with high nucleotide complementarity in mRNA of C2H2, ERF, GRAS TF genes of wheat was shown. All binding sites of these miRNAs were located in the CDS of mRNA target genes. Of the 125 miRNAs of T. aestivum, miR319-3p efficiently bound with mRNA of C2H2 family genes with the value of ΔG/ΔGm equal 91 %. miR7757-5p interacted with mRNA of ERF and GRAS family genes with the value of ΔG/ΔGm equal to 92 % and 90 % respectively. miR9778-5p bound with mRNA of C2H2, ERF, GRAS family genes to varying degrees. Each of the miR408-3p, miR9780-3p, and miR9778-5p had four target genes with the value of ΔG/ΔGm equal to 87 % and 89 %. These data indicate the dependency of C2H2, GRAS, ERF TFs families expression on miRNA. The obtained results expand the fundamental ideas about the regulatory mechanisms of miRNA in the process of plant growth and development.

Serum microRNA profiles among dioxin exposed veterans with monoclonal gammopathy of undetermined significance

ABSTRACTPreviously an increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma (MM), was reported among Vietnam veterans exposed to Agent Orange and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dysregulated expression of certain microRNAs (miRNAs) was demonstrated in MGUS and MM. Given the important role of miRNAs in cellular homeostasis, the aim of this study was to determine if there was an association between serum levels of selected miRNAs and TCDD in 47 MGUS cases identified in our previous investigation using serum specimens and exposure data archived by the Air Force Health Study (AFHS). A total of 13 miRNA levels (let-7a, let-7i, miR-16, miR-20a, miR-21, miR-34a, miR-106b, miR-146a, miR-181a, miR-192, miR-205, miR-335, and miR-361) was measured in serum stored during the 2002 AFHS follow-up and the relationship to lipid-adjusted serum TCDD levels in 1987 was determined. miR-34a showed the strongest relationship with TCDD; after age-adjustment, this positive association was more pronounced. In contrast, the other 12 miRNAs displayed absolute values of age adjusted coefficient estimates below 1.16 and non-significant p-values. The observed strong positive association between high body burdens of TCDD and miR-34a, a tumor suppressor regulated by p53, in this MGUS population warrants clarification of the TCDD-miR-34a relationship and its role in the pathogenesis of MGUS and risk for MM.

Effects of microRNAs polymorphism in cancer progression.

MicroRNAs (miRNAs) are known as a new class of small RNAs (18-25 nucleotides) that regulate gene expression at multiple levels from transcription to translation. Considering the important role of miRNAs in cell proliferation, differentiation, and apoptosis, any variations in their expression can contribute to various anomalies, such as tumorigenesis. Single-nucleotide polymorphisms (SNPs) have received much attention as potential genetic markers for diseases due to their advantage of being present at a high frequency in the human genome. SNPs can occur in different parts of the miRNA genes (primary, precursor, and mature) which result in pathological conditions. In this study, recent findings related to the effects of SNPs in miRNAs on their biogenesis and functions and their role in cancer development and progression are discussed. This review was performed using PubMed to search for related reports. The identified effects may be useful for clinical decision-making and providing important new information about the pathophysiology of miRNAs.

Immune-related miRNA-mRNA regulation network in the livers of DHAV-3-infected ducklings

BackgroundDuck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. However, the molecular mechanism underlying DHAV-3 infection in ducklings remains poorly understood. To study the genetic regulatory network for miRNA-mRNA and the signaling pathways involved in DHAV-3 infection in ducklings, we conducted global miRNA and mRNA expression profiling of duckling liver tissues infected with lethal DHAV-3 by high-throughput sequencing.ResultsWe found 156 differentially expressed miRNAs (DEMs) and 7717 differentially expressed genes (DEGs) in livers of mock-infected and DHAV-3-infected duckling. A total of 19,606 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of these DEMs and DEGs. Moreover, immune-related pathways, including the cytokine-cytokine receptor interaction, apoptosis, Toll-like receptor, Jak-STAT, and RIG-I-like receptor signaling pathway, were significantly enriched through analyzing functions of mRNAs in the network in response to DHAV-3 infection. Furthermore, apl-miR-32-5p, apl-miR-125-5p, apl-miR-128-3p, apl-miR-460-5p, and novel-m0012-3p were identified as potential regulators in the immune-related signaling pathways during DHAV-3 infection. And some host miRNAs were predicted to target the DHAV-3 genome.ConclusionsThis is the first integrated analysis of miRNA and mRNA in DHAV-3-infected ducklings. The results indicated the important roles of miRNAs in regulating immune response genes and revealed the immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver. These findings increase our knowledge of the roles of miRNAs and their target genes in DHAV-3 replication and pathogenesis. They also aid in the understanding of host-virus interactions.

Genes underlying cold acclimation in the tea plant (<i>Camellia sinensis</i> (L.) Kuntze)

The article reviews the latest studies showing the diversity of genetic mechanisms and gene families underlying the increased cold and frost tolerance of tea and other plant species. It has been shown that cell responses to chilling (0…+15°C) and freezing (< 0°C) are not the same and gene expression under cold stress is genotype-specific. In recent decades, progress has been made in understanding the genetic mechanisms underlying the cold response of plants – ICE1 (inducer of CBF expression 1), CBF (C-repeat-binding factor), COR (cold-regulated genes) pathways and signaling have been discovered. The ICE, CBF and DHN gene groups play a key role in the cold acclimation of the tea plant. The accumulation of CBF transcripts occurs after 15 min of chilling induction, and longer cold stress leads to accumulation of CBF transcripts. It is shown that the transcripts of the CsDHN1, CsDHN2 and CsDHN3 genes accumulate at a higher level in resistant genotypes of tea in comparison with susceptible cultivars during freezing. CBF-independent pathways include genes involved in metabolism and transcription factors such as HSFC1, ZAT12, CZF1, PLD (phospholipase D), WRKY, HD-Zip, CsLEA, LOX, NAC, HSP, which are widely distributed in plants and are involved in the basic mechanisms of tea resistance to cold and frost. The most recent studies show an important role of miRNA in the mechanisms of response to chilling and freezing in tea. The data obtained on different plant species may correlate with the mechanisms of frost tolerance of tea and are the basis for future studies of the signaling pathways of response to cold in the tea plant. The results of the research emphasize the need to further explore the ways in which various genes regulate the tolerance of tea to cold stress to find the molecular markers of frost tolerance.

MicroRNAs: Biological Regulators in Pathogen-Host Interactions.

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

Expression of Micrornas 31, 155 and 29C and Their Relation to Pathogenesis and Severity of Alopecia Areata

Alopecia areata (AA) is a common autoimmune disorder that targets anagen hair follicles. The most widely accepted hypothesis in its pathogenesis is that it is a T-cell-mediated autoimmune condition in genetically predisposed individuals. MicroRNAs (miRNAs) are implicated in disease etiology and treatment. Interestingly, miRNAs 31, 155 and 29c have shown an important role in alopecia areata. Since miRNA can be used as serum biomarker in other autoimmune diseases. This study aimed to assess and compare serum levels of miRNAs 31, 155 and 29c in 50 AA patients with their levels in 50 healthy subjects & correlate their levels to severity of AA. Serum levels of miRNAs 31, 155 and 29c were estimated by qRT-PCR technique and miRNAs 31 and 29c were found to be significantly higher in AA patients compared to controls. MicroRNA 155 however, showed no significant difference between serum levels of AA patients compared to controls. These findings suggest the important role of miRNAs 31, 29c and 155 in the pathogenesis of AA.

The potential role of miRNAs in calcification of cardiovascular diseases

MicroRNA is a class of endogenous noncoding 17-25 nucleotides RNAs that regulate gene expression. Recently, more and more works have been appeared confirming the important role of miRNAs in the development and progression of cardiovascular diseases. Calcification mechanisms include impaired regulation of calcium and phosphate metabolism, activation of the signaling pathways that regulate bone formation, and suppression of the signaling pathways responsible for maintaining the smooth muscle cell phenotype. The involvement of microRNAs was demonstrated for each of these mechanisms, which emphasizes the significant contribution of microRNAs to the development of calcification of blood vessels. This review summarizes the scientific data on microRNAs that are proven to be involved in the development of in vitro and in vivo calcification of their targets, as well as the latest achievements in microRNA studies in the context of vascular calcification. We also discuss the possibility of their use for early diagnostics and treatment of calcification in cardiovascular diseases.

Pre-diagnostic role of platelet miRNA in coronary heart disease of healthy overweight subjects via platelet leptin receptor activation

Obesity and overweight have become a global problem that development of various coronary artery diseases (CAD), such as myocardial infarction, atherosclerosis and congestive heart failure. Effective diagnosis is needed for effective treatment and prevention, particularly in healthy overweight subject. Platelets is an important component of hemostatic balance, that maintains the coagulation physiology. Platelets are involved in different pathological events such as thrombosis and CAD in various inflammatory conditions. There are evidences that highlight an important role of miRNA in regulation of gene expression profiling in platelets. Current hypothesis has shown the likelihood of using miRNAs as diagnostic markers in the event of CAD. This review article describes the association between overweight/obesity and platelets activation in elucidating the gene expression profiling in platelet miRNAs in CAD patient. The application of platelet miRNAs as predictive markers in overweight/obese individuals may become a marginal milestone in the history of this diet-related disorder treatment.