Role Of miRNAs In Regulation Research Articles

Advances of miRNA-mediated regulatory roles in plant-microbe interaction

There are many bidirectional communication and crosstalk between microbes and host plants. The plant-pathogen interaction directly affects the survival of host plants, while the interaction between plants and their probiotics benefits both. Plant miRNA responds quickly to pathogenic or beneficial microbes when they enter the plant tissues, while microbes also produce miRNA-like RNA (milRNA) to affect plant health. These means miRNA or milRNA is an important fast-responding molecular mediator in plant-microbe interactions, and these internal mechanisms have been better understood in recent years. This review summarized the regulatory roles of miRNA in plant-pathogens and plant-probiotics interaction. The regulatory role of miRNA in disease resistance of host plants during plant-pathogens interaction, and the regulatory role of miRNA in promoting host growth and development during plant-probiotics interaction, as well as the cross-kingdom regulatory role of milRNA in host plants, were discussed in-depth.

Synaptic plasticity and depression: the role of miRNAs dysregulation.

MicroRNAs (miRNAs) have been recently shown to exert several functional roles in the development and function of neurons. Moreover, numerous miRNAs are present in high abundance in presynaptic and postsynaptic sites regulating synaptic plasticity and activity through different mechanisms. We searched PubMed and Google Scholar databases with key words "Synaptic plasticity", "miRNA" and "major depressive disorder. Synaptic plasticity has an essential role in the ability of the brain to integrate transitory experiences into constant memory traces. Thus, it participates in the development of neuropsychiatric diseases such as major depressive disorder (MDD). Most notably, MDD-related alterations in synaptic function have been found to be closely related with abnormal expression of miRNAs. Several miRNAs such as miR-9-5p, miR-204-5p, miR-128-3, miR-26a-3p, miR-218, miR-22-3p, miR-124-3p, miR-136-3p, miR-154-5p, miR-323a-3p, miR-425-5p, miR-34a, miR-137, miR-204-5p, miR-99a, miR-134, miR-124-3p and miR-3130-5p have been shown to be involved in the regulation of synaptic plasticity in the context of MDD. In the current review, we elaborate the role of miRNAs in regulation of this important neuronal feature in MDD.

Comparison of miRNA and mRNA Expression in Sika Deer Testes With Age.

To elucidate the complex physiological process of testis development and spermatogenesis in Sika deer, this study evaluated the changes of miRNA and mRNA profiles in the four developmental stages of testis in the juvenile (1-year-old), adolescence (3-year-old), adult (5-year-old), and aged (10-year-old) stages. The results showed that a total of 198 mature, 66 novel miRNAs, and 23,558 differentially expressed (DE) unigenes were obtained; 14,918 (8,413 up and 6,505 down), 4,988 (2,453 up and 2,535 down), and 5,681 (2,929 up and 2,752 down) DE unigenes, as well as 88 (43 up and 45 down), 102 (44 up and 58 down), and 54 (18 up and 36 down) DE miRNAs were identified in 3- vs. 1-, 5- vs. 3-, and 10- vs. 5-year-old testes, respectively. By integrating miRNA and mRNA expression profiles, we predicted 10,790 mRNA–mRNA and 69,883 miRNA–mRNA interaction sites. The target genes were enriched by GO and KEGG pathways to obtain DE mRNA (IGF1R, ALKBH5, Piwil, HIF1A, BRDT, etc.) and DE miRNA (miR-140, miR-145, miR-7, miR-26a, etc.), which play an important role in testis development and spermatogenesis. The data show that DE miRNAs could regulate testis developmental and spermatogenesis through signaling pathways, including the MAPK signaling pathway, p53 signaling pathway, PI3K-Akt signaling pathway, Hippo signaling pathway, etc. miR-140 was confirmed to directly target mutant IGF1R-3′UTR by the Luciferase reporter assays. This study provides a useful resource for future studies on the role of miRNA regulation in testis development and spermatogenesis.

MiRNA-Mediated Low Expression of EPHX3 Is Associated with Poor Prognosis and Tumor Immune Infiltration in Head and Neck Squamous Cell Carcinomas.

The aim of this study was to explore the regulatory role of epoxide hydrolase 3 (EPHX3) in head and neck squamous cell carcinoma (HNSCC) and to analyze its bioinformatic function, as well as, to screen and predict the miRNAs that can regulate EPHX3 expression in HNSCC. We examined the expression profile and prognostic potential of EPHX3 in TCGA and GTEX databases and performed functional enrichment analysis of EPHX3 using string database. Subsequently, we analyzed the regulatory role of miRNAs on EPHX3, including expression analysis, correlation analysis, and survival analysis. In addition, we also used TIMER to investigate the relationship among EPHX3 expression level, immune checkpoints, and immune infiltration in HNSCC. The results of data analysis after TGCA showed that EPHX3 is a key regulator of tumorigenesis in 13 cancers and can be used as a marker of poor prognosis in HNSCC patients. Bioinformatics analysis revealed that miR-4713-3p is a key miRNA of EPHX3 in HNSCC. Together, our findings indicate that EPHX3 exerts its anticancer effects by suppressing tumor immune checkpoint expression and immune cell infiltration. Overall, our data uncovered miRNA-mediated EPHX3 downregulation as a contributor to poor HNSCC prognosis and reduced tumor immune infiltration.

The role of miRNAs in regulation of platelet activity and related diseases - a bioinformatic analysis

MicroRNAs (miRNAs) are small, non-coding RNAs, able to regulate cellular functions by induction of mRNA degradation and post-transcriptional repression of gene expression. Platelets are the major source of circulating miRNAs, with significant regulatory potential on cardiovascular pathophysiology and other diseases. MiRNAs have been shown to modify the expression of platelet proteins, which influence the platelets reactivity. Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers as well as therapeutic targets including cardiovascular diseases (CVDs). Herein, we present original results from bioinformatic analyses, which identified top 22 platelet-related miRNAs including hsa-miR-320a, hsa-miR-16-5p, hsa-miR-106a-5p, hsa-miR-320b, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-92a-3p as widely involved in platelet reactivity and associated diseases, including CVDs, Alzheimer’s and cerebrovascular diseases, cancer and hypertension. Analysis focused on the identification of the highly regulatory targets shared between those miRNAs identified 43 of them. Best ranked genes associated with overall platelet activity and most susceptible for noncoding regulation were PTEN, PIK3R1, CREB1, APP, and MAPK1. Top targets also strongly associated with CVDs were VEGFA, IGF1, ESR1, BDNF, and PPARG. Top targets associated with other platelet-related diseases including cancer identified in our study were TP53, KRAS, and CCND1. The most affected pathways by top miRNAs and top targets included diseases of signal transduction by Growth Factor Receptors (GDFRs) and second messengers, platelet activation, signaling, and aggregation, signaling by VEGF, MAPK family signaling cascades, and signaling by Interleukins. Terms specific only for platelet-related miRNAs included coronary artery disease, platelet degranulation, and neutrophil degranulation, while for the top platelet-related genes it was Estrogen Signaling Receptor (ESR) mediated signaling, extra-nuclear estrogen signaling, and endometriosis. Our results show the novel features of platelet physiology and may provide a basis for further clinical studies focused on platelet reactivity. They also show in which aspects miRNAs can be promising biomarkers of platelet-related pathological processes.

Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation

FBLN5, a member of the short fibulins in the fibulin family of extracellular matrix/matricellular proteins, is involved in interactions with components of the basement membrane and extracellular matrix proteins. It plays key roles in endothelial tissues in many vascular diseases. In this study, the relationship between FBLN5 and carotid atherosclerotic plaque stability as well as the regulatory roles of miRNAs were evaluated. Differential gene expression analyses and weighted gene co-expression network analysis (WGCNA) based on the GSE163154 dataset (including 16 samples without intraplaque hemorrhage and 27 samples with intraplaque hemorrhage) in GEO revealed that FBLN5 is related to plaque stability and is the most significantly differentially expressed gene. LASSO regression was used to evaluate genes obtained from the intersection of differentially expressed genes and clinically significant modules identified by WGCNA. A prediction model based on eight genes, including FBLN5, was constructed and showed an accuracy of 0.951 based on an ROC analysis. Low FBLN5 expression in plaque tissues was confirmed by immunohistochemistry and western blotting. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that FBLN5 acted mainly by the maintenance of the cellular matrix and reactive oxygen species production. miRNAs upstream of these eight predictive genes, including FBLN5, were identified and used to construct a network diagram. These results revealed that hsa-mir-128 and hsa-mir-532–3p were upstream regulatory factors of FBLN5, as verified by PCR assays of human plaque tissues demonstrating that both miRNAs were significantly up-regulated. Therefore, FBLN5 may play an important role in carotid atherosclerosis via hsa-mir-128 and hsa-mir-532–3p as well as become an essential target for treatment.

Difference in miRNA Expression in Functioning and Silent Corticotroph Pituitary Adenomas Indicates the Role of miRNA in the Regulation of Corticosteroid Receptors.

Corticotroph pituitary adenomas commonly cause Cushing’s disease (CD), but some of them are clinically silent. The reason why they do not cause endocrinological symptoms remains unclear. We used data from small RNA sequencing in adenomas causing CD (n = 28) and silent ones (n = 20) to explore the role of miRNA in hormone secretion and clinical status of the tumors. By comparing miRNA profiles, we identified 19 miRNAs differentially expressed in clinically functioning and silent corticotroph adenomas. The analysis of their putative target genes indicates a role of miRNAs in regulation of the corticosteroid receptors expression. Adenomas causing CD have higher expression of hsa-miR-124-3p and hsa-miR-135-5p and lower expression of their target genes NR3C1 and NR3C2. The role of hsa-miR-124-3p in the regulation of NR3C1 was further validated in vitro using AtT-20/D16v-F2 cells. The cells transfected with miR-124-3p mimics showed lower levels of glucocorticoid receptor expression than control cells while the interaction between miR-124-3p and NR3C1 3′ UTR was confirmed using luciferase reporter assay. The results indicate a relatively small difference in miRNA expression between clinically functioning and silent corticotroph pituitary adenomas. High expression of hsa-miR-124-3p in adenomas causing CD plays a role in the regulation of glucocorticoid receptor level and probably in reducing the effect of negative feedback mediated by corticosteroids.

Four MicroRNAs, miR-13b-3p, miR-278-5p, miR-10483-5p, and miR-10485-5p, Mediate Insecticide Tolerance in Spodoptera frugiperda.

Spodoptera frugiperda is the world’s major agricultural pest and has the distinctive features of high fecundity, strong migratory capacity, and high resistance to most insecticides. At present, the control of S. frugiperda in China relies mainly on the spraying of chemical insecticides. MicroRNAs (miRNAs) are a class of small, single-stranded, non-coding RNAs and play crucial regulatory roles in various physiological processes, including the insecticide resistance in insects. However, little is known about the regulatory roles of miRNAs on the resistance of S. frugiperda to insecticides. In the present research, the miRNAs that were differentially expressed after cyantraniliprole, spinetoram, and emamectin benzoate treatment were analyzed by RNA-Seq. A total of 504 miRNAs were systematically identified from S. frugiperda, and 24, 22, and 31 miRNAs were differentially expressed after treatments of cyantraniliprole, spinetoram, and emamectin benzoate. GO and KEGG enrichment analyses were used to predict the function of differentially expressed target genes of miRNAs. Importantly, ten miRNAs were significantly differentially expressed among the treatments of three insecticides. miR-278-5p, miR-13b-3p, miR-10485-5p, and miR-10483-5p were significantly downregulated among the treatments of three insecticides by RT-qPCR. Furthermore, the overexpression of miR-278-5p, miR-13b-3p, miR-10485-5p, and miR-10483-5p significantly increased the mortality of S. frugiperda to cyantraniliprole and emamectin benzoate. The mortality was significantly increased with spinetoram treatment after the overexpression of miR-13b-3p, miR-10485-5p, and miR-10483-5p. These results suggest that miRNAs, which are differentially expressed in response to insecticides, may play a key regulatory role in the insecticide tolerance in S. frugiperda.

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.

Regulation of Runx2 and Its Signaling Pathways by MicroRNAs in Breast Cancer Metastasis.

As a major threat among women globally, breast cancer (BC) emerges as a primary research focus for several researchers. Although various therapeutic regimens are available, there is an increased chance of metastasis of BC cells, which raises the severity of this malignancy. Of multiple preferred secondary targets, metastasis to bone is extensively studied. Besides deemed as a bone transcription factor, Runx2 also acts as a metastatic factor that promotes growth and metastasis of BC cells. Studies have reported the significant role of microRNAs (miRNAs) in BC pathogenesis and metastasis by governing Runx2 expression. Additionally, dysregulation of the signaling pathways, including Wnt/β-catenin, TGF-β, Notch, and PI3K/AKT, has been observed to influence the expression of Runx2 in BC cells. In this review, we have aimed to highlight the regulatory role of miRNAs in targeting Runx2 both directly and indirectly by governing respective signaling pathways during bone metastasis of BC.

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.

The Diagnostic, Prognostic and Therapeutic Role of miRNAs in Adrenocortical Carcinoma: A Systematic Review.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis and a high rate of recurrence and mortality. Therapeutic options are limited. In some cases, the distinction of ACCs from benign adrenal neoplasms with the existing widely available pathological and histopathological tools is difficult. Thus, new biomarkers have been tested. We conducted a review of the recent literature on the advances of the diagnostic, prognostic and therapeutic role of miRNAs on ACC patients. More than 10 miRNAs validated by multiple studies were found to present a diagnostic and prognostic role for ACC patients, from which miR-483-5p and miR-195 were the most frequently met biomarkers. In particular, upregulation of miR-483-5p and downregulation of miR-195 were the most commonly validated molecular alterations. Unfortunately, data on the therapeutic role of miRNA are still scarce and limited mainly at the experimental level. Thus, the role of miRNA regulation in ACC remains an area of active research.

Small RNA profiling for identification of microRNAs involved in regulation of seed development and lipid biosynthesis in yellowhorn

BackgroundYellowhorn (Xanthoceras sorbifolium), an endemic woody oil-bearing tree, has become economically important and is widely cultivated in northern China for bioactive oil production. However, the regulatory mechanisms of seed development and lipid biosynthesis affecting oil production in yellowhorn are still elusive. MicroRNAs (miRNAs) play crucial roles in diverse aspects of biological and metabolic processes in seeds, especially in seed development and lipid metabolism. It is still unknown how the miRNAs regulate the seed development and lipid biosynthesis in yellowhorn.ResultsHere, based on investigations of differences in the seed growth tendency and embryo oil content between high-oil-content and low-oil-content lines, we constructed small RNA libraries from yellowhorn embryos at four seed development stages of the two lines and then profiled small RNA expression using high-throughput sequencing. A total of 249 known miRNAs from 46 families and 88 novel miRNAs were identified. Furthermore, by pairwise comparisons among the four seed development stages in each line, we found that 64 miRNAs (53 known and 11 novel miRNAs) were differentially expressed in the two lines. Across the two lines, 15, 11, 10, and 7 differentially expressed miRNAs were detected at 40, 54, 68, and 81 days after anthesis, respectively. Bioinformatic analysis was used to predict a total of 2654 target genes for 141 differentially expressed miRNAs (120 known and 21 novel miRNAs). Most of these genes were involved in the fatty acid biosynthetic process, regulation of transcription, nucleus, and response to auxin. Using quantitative real-time PCR and an integrated analysis of miRNA and mRNA expression, miRNA-target regulatory modules that may be involved in yellowhorn seed size, weight, and lipid biosynthesis were identified, such as miR172b-ARF2 (auxin response factor 2), miR7760-p3_1-AGL61 (AGAMOUS-LIKE 61), miR319p_1-FAD2–2 (omega-6 fatty acid desaturase 2–2), miR5647-p3_1-DGAT1 (diacylglycerol acyltransferase 1), and miR7760-p5_1-MED15A (Mediator subunit 15a).ConclusionsThis study provides new insights into the important regulatory roles of miRNAs in the seed development and lipid biosynthesis in yellowhorn. Our results will be valuable for dissecting the post-transcriptional and transcriptional regulation of seed development and lipid biosynthesis, as well as improving yellowhorn in northern China.

Regulation of airway immunity by epithelial miRNAs.

The airway epithelium is essential to protect the host from inhaled pathogens and particles. It maintains immune homeostasis and mediates tissue repair after injury. Inflammatory diseases of the airways are associated with failure of epithelial functions, including loss of barrier integrity that results in increased tissue permeability and immune activation; excessive mucus secretion and impaired mucociliary clearance that leads to airflow obstruction and microbial overgrowth; and dysregulation of cellular signals that promotes inflammation and alters tissue structure and airway reactivity. MicroRNAs play crucial roles in mounting appropriate cellular responses to environmental stimuli and preventing disease, using a common machinery and mechanism to regulate gene expression in epithelial cells, immune cells of hematopoietic origin, and other cellular components of the airways. Respiratory diseases are accompanied by dramatic changes in epithelial miRNA expression that drive persistent immune dysregulation. In this review, we discuss responses of the epithelium that promote airway immunopathology, with a focus on miRNAs that contribute to the breakdown of essential epithelial functions. We emphasize the emerging role of miRNAs in regulation of epithelial responses in respiratory health and their value as diagnostic and therapeutic targets.

Identification of miRNAs mediating shoot growth of grafted sweet cherry through small RNA and degradome sequencing

Sweet cherry (Prunus avium L) is an economically important fruit tree in the worldwide, in which grafting is widely used for plant propagation. Rootstock plays a vital role in shoot growth. However, thus far there have been few reports concerning the molecular mechanism of how rootstock regulates scion growth. MicroRNAs (miRNAs) are crucial small RNAs involved in multiple biological processes. The regulatory roles of miRNAs in the grafting of sweet cherry are not yet clear. In the current work, twelve libraries were constructed using the leaves and stems of sweet cherry grafted on two types of Chinese cherry (Prunus pseudocerasus) rootstocks by high-throughput sequencing. A total of 238 known miRNAs were cataloged into 61 families, and 40 novel ones were identified. Among these miRNAs, 13 and 21 miRNAs were differentially expressed in leaves and stems, respectively. The degradome results and prediction analysis of differentially expressed miRNAs and their targets indicated that miRNAs mediate the growth of scion via several aspects: the shoot apical meristem development, phytohormone synthesis and signal transduction, the absorption and balance of nutrient elements. The available evidence facilitates a better understanding of the role of miRNAs in the response of sweet cherry scion to Chinese cherry rootstock after grafting.

MicroRNAs in Genetic Etiology of Human Diseases.

Since their first discovery more than 20years ago, miRNAs have been subject to deliberate research and analysis for revealing their physiological or pathological involvement. Regulatory roles of miRNAs in signal transduction, gene expression, and cellular processes in development, differentiation, proliferation, apoptosis, and homeostasis also imply their critical role in disease pathogenesis. Their roles in cancer, neurodegenerative diseases, and other systemic diseases have been studied broadly. In these regulatory pathways, their mutations and target sequence variations play critical roles to determine their functional repertoire. In this chapter, we summarize studies that investigated the role of mutations, polymorphisms, and other variations of miRNAs in respect to pathological processes.

GH and IGF System: The Regulatory Role of miRNAs and lncRNAs in Cancer.

Growth hormone (GH) and the insulin-like growth factor (IGF) system are involved in many biological processes and have growth-promoting actions regulating cell proliferation, differentiation, apoptosis and angiogenesis. A recent chapter in epigenetics is represented by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) which regulate gene expression. Dysregulated miRNAs and lncRNAs have been associated with several diseases including cancer. Herein we report the most recent findings concerning miRNAs and lncRNAs regulating GH and the IGF system in the context of pituitary adenomas, osteosarcoma and colorectal cancer, shedding light on new possible therapeutic targets. Pituitary adenomas are increasingly common intracranial tumors and somatotroph adenomas determine supra-physiological GH secretion and cause acromegaly. Osteosarcoma is the most frequent bone tumor in children and adolescents and was reported in adults who were treated with GH in childhood. Colorectal cancer is the third cancer in the world and has a higher prevalence in acromegalic patients.

Genome-Wide Expression Difference of MicroRNAs in Basal Cell Carcinoma.

Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin (n = 15; control group) and tissues at tumor centers from patients with cheek BCC (n = 15; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the “basal cell carcinoma pathways” were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis.

MicroRNA-223 inhibits neutrophil extracellular traps formation through regulating calcium influx and small extracellular vesicles transmission

Modulation of miRNAs and neutrophil extracellular traps (NETs) formation are both implicated in inflammatory disorders. Adult-onset Still’s disease (AOSD) is a systemic autoinflammatory disease with neutrophilic leukocytosis and unknown etiology. Although the NETs formation is elevated in AOSD patients, the regulatory roles of miRNAs in NETs formation in AOSD remains unclear. We revealed that the circulating levels of IL-18, NETs, and miR-223 were significantly higher in active AOSD patients, compared with inactive AOSD patients or healthy controls (P < 0.005). Moreover, IL-18 increased calcium influx into neutrophils, which led to mitochondrial ROS (mROS) production and NETs formation. Elevated levels of NETs-DNA could induce miR-223 expression in neutrophils through activating Toll-like receptor 9. The upregulated miR-223 expression in neutrophils suppressed mROS production by blocking calcium influx, and subsequently inhibited IL-18-mediated NETs formation. Besides, the increased neutrophil-derived exosomal miR-223 levels were observed in active AOSD patients compared with healthy controls (P < 0.005). Our in vitro assays demonstrated that the neutrophil-derived small extracellular vesicles carried miR-223, which could repress IL-18 production in macrophages. Together, these results suggest a fine-tuned mechanism between inflammatory (IL-18 induced NETs) and anti-inflammatory (miR-223) factors in AOSD. MiR-223, mROS inhibitors, and calcium channel blockers are the potential therapeutics for autoinflammatory diseases such as AOSD.

Study of microRNA Expression Profile in Different Regions of Ram Epididymis.

The regional expression of epididymal genes provides a guarantee for sperm maturation. As a class of endogenous non-coding small RNAs, microRNAs (miRNAs) play an important role in spermatogenesis, maturation and fertilization. Currently, the regulatory role of miRNA in the epididymis is poorly understood. Here, transcriptome sequencing was used to analyse miRNA expression profiles in three regions of the epididymis of rams, including caput, corpus and cauda. The results showed that there were 13 known miRNAs between the caput and corpus controls, 29 between the caput and cauda and 22 differences between the corpus and cauda. Based on the analysis of miRNA target genes by GO and KEGG, a negative regulation network of miRNA-mRNA was constructed in which let-7, miR-541-5p, miR-133b and miR-150 may play an important regulatory role in the maturation regulation of ram epididymal sperm. This research provides a reference for studying the regulation mechanism of sperm maturation in male epididymis and improving semen quality and male reproductive performance.