miRNA Function Research Articles

MiR-155-1 as a positive factor for novel duck reovirus replication by regulating SOCS5-mediated interferons

Diseases caused by novel duck reovirus (NDRV) have brought considerable economic losses to the poultry industry. MicroRNAs (miRNAs) have an impact on virus replication and antiviral immunity. However, the miRNA profile upon NDRV infection in duck embryo fibroblasts (DEFs) remains to be discovered. In this study, small RNA (sRNA) sequencing was performed to decipher the cellular miRNA response to NDRV infection. Based on 26 differentially expressed miRNAs (19 upregulated and 7 downregulated miRNAs) obtained from sequencing data and their target genes predicted by software, GO and KEGG analyses were performed to elucidate the functions of miRNAs in NDRV invasion, replication, and virus spread. “FoxO signaling pathway”, “autophagy”, and “Toll-like receptor signaling pathway” might participate in NDRV replication as revealed by KEGG enrichment analysis. The miR-155-1 sequence was found to be identical to rno-miR-155-5p and was sharply increased with the progression of NDRV infection. Moreover, NDRV-induced miR-155-1 could act as a positive factor for virus replication in DEFs, which inhibited type I interferon (IFN-I) production. Luciferase assay confirmed that miR-155-1 disturbed the abundance of suppressor of cytokine signaling (SOCS) 5 by targeting 3’-UTR. SOCS5, which is linked to increased IRF7 expression, restricts IFN expression and promotes NDRV replication in DEFs. Therefore, this study proposed that miR-155-1 was used by NDRV to restrict SOCS5 expression, attenuating the production of IFN-I and creating a favorable environment for virus replication.

Modulation of MicroRNA Expression During In Vitro Chondrogenesis.

Since their discovery in 1993, microRNAs (miRNAs) are now recognized as important epigenetic regulators of many mammalian cellular processes including proliferation, apoptosis, metabolism, and differentiation. These small non-coding RNAs function by interacting with specific regions in the 3'-untranslated region of mRNAs, thereby resulting in mRNA degradation or suppression of translation. Since miRNAs have the ability to target many mRNAs within a given cell type, a number of cellular pathways and networks may be regulated as a result. To study the function of miRNAs, a number of methods can be used to modulate their activity in cells such as synthetic mimics or antagomirs for short-term assays or viral-based approaches for longer-term experiments such as cell differentiation assays. In this chapter, we provide our methodology to constitutively overexpress a desired miRNA during in vitro chondrogenesis of human cartilage progenitor cells (CPCs). Specifically, we describe how we obtain CPCs from human articular cartilage specimens, how we generate and titrate lentivirus engineered to overexpress a precursor miRNA, how we transduce CPCs with lentivirus and differentiate them toward the chondrocyte lineage, and how we extract RNA and measure expression levels of the miRNA of interest during in vitro chondrogenesis. We also provide some data from our laboratory demonstrating that we can achieve and maintain miRNA overexpression for up to 14days in cartilage pellet cultures. We predict that these lentiviral-based approaches will also be useful to study how miRNA modulation of progenitor cells affects cell differentiation and extracellular matrix production within three-dimensional biomaterial scaffolds.

High-Throughput Analysis Reveals miRNA Upregulating α-2,6-Sialic Acid through Direct miRNA-mRNA Interactions.

Chemical biology has revealed the importance of sialic acids as a major signal in physiology and disease. The terminal modification α-2,6-sialic acid is controlled by the enzymes ST6GAL1 and ST6GAL2. Dysregulation of this glycan impacts immunological recognition and cancer development. microRNAs (miRNA, miR), noncoding RNAs that downregulate protein expression, are important regulators of glycosylation. Using our recently developed high-throughput fluorescence assay (miRFluR), we comprehensively mapped the miRNA regulatory landscape of α-2,6-sialyltransferases ST6GAL1 and ST6GAL2. We found, contrary to expectations, the majority of miRNAs upregulate ST6GAL1 and α-2,6-sialylation in a variety of cancer cells. In contrast, miRNAs that regulate ST6GAL2 were predominantly downregulatory. Mutational analysis identified direct binding sites in the 3'-untranslated region (UTR) responsible for upregulation, confirming it is a direct effect. The miRNA binding proteins AGO2 and FXR1 were required for upregulation. Our results upend common assumptions surrounding miRNA, arguing that upregulation by these noncoding RNA is common. Indeed, for some proteins, upregulation may be the dominant function of miRNA. Our work also suggests that upregulatory miRNAs enhance overexpression of ST6GAL1 and α-2,6-sialylation, providing another potential pathway to explain the dysregulation observed in cancer and other disease states.

Sensing miRNAs for Disease Diagnostics

AbstractmiRNAs are short nucleic acid sequences that regulate gene expression and are important biomarkers for disease diagnostics. In this Review, we overview the biogenesis and functions of miRNAs. The recent progress of biomarker development based on miRNAs is further discussed. In the end, we summarize the progress on miRNA detection methods towards clinical diagnostics. Although proper tools and standardized methodology in detection are still the bottlenecks for miRNA‐based diagnosis, the challenges are likely to be overcome with the development of new bioanalytical techniques. More importantly, upstream studies to elucidate mechanisms of miRNAs in target recognition and correlation with diseases will further advance the clinical use of miRNAs as biomarkers.

Abstract 15321: MicroRNA Mir-378-3p is a Novel Regulator of Endothelial Autophagy and Function

Introduction: Autophagy maintains cellular homeostasis by degradation of unnecessary proteins for their recycling and reuse. MicroRNAs (miRNAs) regulate various biological processes including autophagy. MiRNA and autophagy both regulate endothelial function, however, role of miRNAs in endothelial autophagy and function is unknown. Methods and Results: To understand the role of miRNAs in endothelial autophagy, autophagy was genetically inhibited via ATG7 (autophagy-related gene 7) silencing in Human Umbilical Vein Endothelial Cells (HUVECs) and then a miRNA array was performed, which showed miR-378-3p as the most up-regulated miRNA. Pharmacological (via chloroquine treatment) inhibition of autophagy in HUVECs resulted in significant upregulation of miR-378a-3p. Autophagy activation via starvation in HUVECs significantly reduced miR-378a-3p expression. Next, we over-expressed miR-378a-3p (via mimic) in HUVECs and measured autophagy and endothelial function. MiR-378a-3p overexpression was associated with impaired autophagy (reduced LC3-II/LC3-I ratio), reduced proliferation, and increased migration in HUVECs. At the molecular level, miR-378a-3p overexpression was associated with reduced eNOS expression at both transcript and protein levels in HUVECs. MiR-378a-3p inhibition (via antagomir) led to reduced cell migration and upregulation of eNOS in HUVECs. In-silico study identified PDIA4 as a potential target of miR-378-3p, and our qPCR data and immunoblotting data confirmed increased and reduced PDIA4 expression in mimics and antagomir-transfected HUVECs, respectively. We then inhibited autophagy using chloroquine (50uM) and observed significantly reduced PDIA4 expression. Inhibition of PDIA4 expression via silencing inhibited autophagic flux indicated by reduced LC3-II/LC3-I in HUVECs. Conclusions: Our findings, for the first time, show an inverse relationship between miR-378a-3p expression and endothelial autophagy and endothelial function. PDIA4 was identified as a molecular target for miR-378a-3p in endothelial cells, which revealed PDIA4’s potential role in endothelial autophagy. Our data demonstrate that miR-378-3p regulates endothelial autophagy and function via modulating PDIA4 expression.

Abstract 15319: Left Ventricular Assistant Device (lvad) Support Did Not Alter Mirna Expression in Heart Failure Patients

Introduction: Micro RNAs (miRNA) are crucial regulators of various biological processes including the pathogenesis of heart failure (HF). In this study, miRNA profiling was compared with pre and post LVAD and non-failing (NF) control heart patients. Our goal was to identify miRNAs involved in HF and responses to LVAD therapy. Methods: Myocardial RNAs were isolated from non-ischemic dilated cardiomyopathy patients (n=22) who went through LVAD placement (pre LVAD) and later transplant (post LVAD) along with 6 normal hearts as controls. NanoString technology was used to quantify miRNA expressions. NanoString miRNAs raw count data were preprocessed and normalized using solver 4.0 Analysis Software. Ingenuity Pathway Analysis (IPA) was done by differentially expressed miRNA to understand the biological pathways involved. Results: Our sample population exhibited 80% male and 95% Caucasian with an average age of 57 and ejection fraction was less than 25% at the time of LVAD placement. The average LVAD duration of patients was 525 days. One ninety-five miRNAs in pre and 120 miRNAs in post LVAD patients were differentially expressed compared to control using cutoff of for the FDR adjusted p-value 0.05 and at least 2-fold changes. There was no significant change in miRNA expression when post LVAD was compared with pre LVAD patients. IPA analysis revealed that there are 15 up-regulated miRNA that promote apoptosis with a net Z score of 2.155 in post LVAD versus control. There are 27 miRNAs with a net of apoptotic with a Z score 0f 0.766 in pre LVAD versus control. It was also noticed from IPA analysis that expression of 8 identical miRNAs in both pre and post LVAD patients were involved in heart fibrosis. LVAD therapy did not change the miRNA expression Conclusions: Our results identify many miRNAs that are associated with apoptosis and fibrosis in end stage heart failure. Molecular mechanisms of heart disease will be identified by miRNA profiling and function as potential biomarkers or therapeutic targets in future. LVAD therapy does not substantially reverse these epigenetic changes in this population.

Multiple Functions of MiRNAs in Brassica napus L.

The worldwide climate changes every year due to global warming, waterlogging, drought, salinity, pests, and pathogens, impeding crop productivity. Brassica napus is one of the most important oil crops in the world, and rapeseed oil is considered one of the most health-beneficial edible vegetable oils. Recently, miRNAs have been found and confirmed to control the expression of targets under disruptive environmental conditions. The mechanism is through the formation of the silencing complex that mediates post-transcriptional gene silencing, which pairs the target mRNA and target cleavage and/or translation inhibition. However, the functional role of miRNAs and targets in B. napus is still not clarified. This review focuses on the current knowledge of miRNAs concerning development regulation and biotic and abiotic stress responses in B. napus. Moreover, more strategies for miRNA manipulation in plants are discussed, along with future perspectives, and the enormous amount of transcriptome data available provides cues for miRNA functions in B. napus. Finally, the construction of the miRNA regulatory network can lead to the significant development of climate change-tolerant B. napus through miRNA manipulation.

The Role of MicroRNAs in Dilated Cardiomyopathy: New Insights for an Old Entity.

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and systolic dysfunction. In most cases, DCM is progressive, leading to heart failure (HF) and death. This cardiomyopathy has been considered a common and final phenotype of several entities. DCM occurs when cellular pathways fail to maintain the pumping function. The etiology of this disease encompasses several factors, such as ischemia, infection, autoimmunity, drugs or genetic susceptibility. Although the prognosis has improved in the last few years due to red flag clinical follow-up, early familial diagnosis and ongoing optimization of treatment, due to its heterogeneity, there are no targeted therapies available for DCM based on each etiology. Therefore, a better understanding of the mechanisms underlying the pathophysiology of DCM will provide novel therapeutic strategies against this cardiac disease and their different triggers. MicroRNAs (miRNAs) are a group of small noncoding RNAs that play key roles in post-transcriptional gene silencing by targeting mRNAs for translational repression or, to a lesser extent, degradation. A growing number of studies have demonstrated critical functions of miRNAs in cardiovascular diseases (CVDs), including DCM, by regulating mechanisms that contribute to the progression of the disease. Herein, we summarize the role of miRNAs in inflammation, endoplasmic reticulum (ER) stress, oxidative stress, mitochondrial dysfunction, autophagy, cardiomyocyte apoptosis and fibrosis, exclusively in the context of DCM.

Dynamic interplay of microRNA in diseases and therapeutic.

MicroRNAs are the major class of small non-coding RNAs, evolutionary conserved post-transcriptional regulators of gene expression. Since their discovery in 1993, they have been implicated as master regulators in numerous cellular processes. MicroRNA (miRNA)s regulate gene expression by attenuation and/or mRNA degradation and are commonly associated with cell development, differentiation, and homeostasis. Extensive research in past two decades has provided new insights into the potential implications of miRNA in the onset, progression, and therapeutic nature of miRNAs in disease manifestation. Owing to the novel discoveries, "miRNAs" would probably pave a new direction in therapeutic research. However, "micro" in length miRNAs have attracted considerable attention in numerous other fields. Understanding the functionality of miRNAs, in this review article, we discussed the mechanistic role of miRNAs in human diseases and have outlined most of the recent published work in clinical therapeutics. We have constructed different network models for miRNA and its targets which made us understand their interrelationship and association with diseases. Future research would surely overcome challenges and would introduce new strategies for the utility of miRNAs in a broader setting.

Degradome Assisted Plant MicroRNA Prediction Under Alternative Annotation Criteria.

Current microRNA (miRNA) prediction methods are generally based on annotation criteria that tend to miss potential functional miRNAs. Recently, new miRNA annotation criteria have been proposed that could lead to improvements in miRNA prediction methods in plants. Here, we investigate the effect of the new criteria on miRNA prediction in Arabidopsis thaliana and present a new degradome assisted functional miRNA prediction approach. We investigated the effect by applying the new criteria, and a more permissive criteria on miRNA prediction using existing miRNA prediction tools. We also developed an approach to miRNA prediction that is assisted by the functional information extracted from the analysis of degradome sequencing. We demonstrate the improved performance of degradome assisted miRNA prediction compared to unassisted prediction and evaluate the approach using miRNA differential expression analysis. We observe how the miRNA predictions fit under the different criteria and show a potential novel miRNA that has been missed within Arabidopsis thaliana. Additionally, we introduce a freely available software 'PAREfirst' that employs the degradome assisted approach. The study shows that some miRNAs could be missed due to the stringency of the former annotation criteria, and combining a degradome assisted approach with more permissive miRNA criteria can expand confident miRNA predictions.

Relationship between the microRNAs and PI3K/AKT/mTOR axis: Focus on non-small cell lung cancer.

Lung cancer (LC) is one of the significant causes of mortality worldwide. It has been reported that several factors, including late diagnosis, cancer recurrence, lack of access to effective treatments, and especially chemo-resistance, negatively impact the clinical outcome of the available therapeutic regimens. MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs, which have been demonstrated to be involved in different aspects of cancer pathogenesis, some of which are known as tumor suppressors, and others may have a role in cancer development or progression. One of the most prominent targets of miRNAs in cancer is the phosphoinositide 3-kinases (PI3Ks)/AKT serine/threonine kinase pathway, which is well-known for regulating the cell cycle and several biological phenomena such as cell proliferation, locomotion, survival, metabolism, and protein synthesis. One group activates the PI3K/AKT pathway axis targeting miRNAs, and the other inhibits this axis. Evidence demonstrated that miRNAs could be employed for diagnosis, treatment monitoring and survival evaluation. Moreover, miRNA-based therapeutic approaches can be helpful in clinical settings of cancer therapy. Therefore, this review summarized the functions of different miRNAs associated with the PI3K/AKT pathway, focusing on non-small cell lung cancer (NSCLC) according to their anti-tumor or oncogenic roles, as well as available and possible therapeutic approaches.

Latest Findings on MicroRNAs in Diabetic Chronic Wounds

Diabetic chronic wound is one of the most serious complications of diabetes, imposing enormous socioeconomic burdens on diabetic patients, their families, and society due to its refractory nature. MicroRNAs (miRNAs) have emerged as important regulators of various physiological and pathological processes. Abnormalities arise in the regulatory functions of miRNAs in chronic diabetic wounds. Therefore, the modification of miRNAs expression in diabetic wounds is an important channel for the improvement of wound healing. The clinical translation of miRNA-based therapy may become a prospective direction of diabetic wound healing. However, miRNA-based therapy is still in its early stage of development, and actual translation into clinical application will take a long time. Herein, we summarized the latest research findings on miRNAs in diabetic chronic wounds healing.

Genetics and epigenetics in conventional chondrosarcoma with focus on non-coding RNAs.

The detection of mutations of isocitrate dehydrogenase 1 and 2 (IDH 1/2) as tumor driver genes in chondromas and chondrosarcomas more than ten years ago was a first major step for better understanding the molecular carcinogenenesis of these rare mesenchymal tumors. Within the TCA cycle, wild-typ IDH1/2 catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). IDH mutations catalyze the production of a non-physiological metabolite, D-2hydroxyglutarate (D-2HG) from α-KG. D-2HG can inhibit the class of α-KG-dependent enzymes by binding competitively to its receptor. Important enzyme families, such as the Ten-Eleven Translocation (TET) family of 5-methylcytosine hydroxylases and the Jumonji family of histone lysine demethylases are α-KG dependent. Many of the TET and Jumonji family-dependent enzymes regulate epigenetic factors, such as DNA methylation, histone modification, and nucleosome remodeling, underscoring the central role of the epigenome in cancer development. When D-2HG acts with these enzymes instead α-KG their functions will be in disarray with heavily hypermethylated DNA and dysregulations in histone metylation. NcRNAs have increasingly been described as a cornerstone of cancer development. Therefore this review describes exemplarily the oncogenic functions of miRNAs in chondrosarcoma in more detail. Particularly in chondrosarcomas additional carcinogenic features are aquired by interactions of ncRNAs with α-KG-dependent epigenetic regulators. Distinct ncRNAs, miRNAs and lncRNAs alike, are involved in deregulating important cellular signalling pathways and thus contributing further to malignant transformation and development of malignant cellular traits in these rare mesenchymal tumors. This review specially empasizes the complex interactions between the world of ncRNAs and genetics and epigenetics.

MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis

Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS. To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin "ClueGO2.5.6". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics. First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis. Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p. Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.

Circulating metals, leukocyte microRNAs and microRNA networks: A profiling and functional analysis in Chinese adults.

Metals in the human body represent both environmental exposure and nutritional status. Little is known about the miRNA signature in relation to circulating metals in humans. To characterize metal-associated miRNAs in leukocytes, individually and collectively as networks. In a panel of 160 Chinese adults, we measured 23 metals/metalloids in plasma, and sequenced miRNAs and mRNAs in leukocytes. We used linear regression to model the associations between ln-transformed metal concentrations and normalized miRNA levels adjusting for potential confounders. We inferred the enriched leukocyte subtypes for the identified miRNAs using an association approach. We utilized mRNA sequencing data to explore miRNA functions. We also constructed modules to identify metal-associated miRNA networks. We identified 55 metal-associated miRNAs at false discovery rate-adjusted P<0.05. In particular, we found that lead, nickel, and vanadium were positively associated with potentially lymphocyte-enriched miR-142-3p, miR-150-3p, miR-28-5p, miR-361-3p, and miR-769-5p, and were inversely associated with potentially granulocyte-enriched let-7a/c/d-5p and miR-1294. Interestingly, the five lymphocyte-enriched miRNAs inhibited, whereas miR-1294 activated, ROS and DNA repair pathways. We further confirmed the findings using oxidative damage biomarkers. Next, we clustered co-expressed miRNAs into modules, and identified four miRNA modules that were associated with different metals. The identified modules represented miRNAs enriched in different leukocyte subtypes, and were involved in biological processes including hematopoiesis and immune response, mitochondrial functions, and response to the stimulus. At commonly exposed low levels, circulating metals were associated with distinct miRNA signatures in leukocytes. The identified miRNAs, individually or as regulatory networks, may provide a mechanistic link between metal exposure and pathophysiological changes in the immune system.

In Vivo Treatment with a Standardized Green Tea Extract Restores Cardiomyocyte Contractility in Diabetic Rats by Improving Mitochondrial Function through SIRT1 Activation.

Background. Green tea catechins are known to promote mitochondrial function, and to modulate gene expression and signalling pathways that are altered in the diabetic heart. We thus evaluated the effectiveness of the in vivo administration of a standardized green tea extract (GTE) in restoring cardiac performance, in a rat model of early streptozotocin-induced diabetes, with a focus on the underlying mechanisms. Methods. Twenty-five male adult Wistar rats were studied: the control (n = 9), untreated diabetic animals (n = 7) and diabetic rats subjected to daily GTE administration for 28 days (n = 9). Isolated ventricular cardiomyocytes were used for ex vivo measurements of cell mechanics and calcium transients, and molecular assays, including the analysis of functional protein and specific miRNA expression. Results. GTE treatment induced an almost complete recovery of cardiomyocyte contractility that was markedly impaired in the diabetic cells, by preserving mitochondrial function and energy availability, and modulating the expression of the sarcoplasmic reticulum calcium ATPase and phospholamban. Increased Sirtuin 1 (SIRT1) expression and activity substantially contributed to the observed cardioprotective effects. Conclusions. The data supported the hypothesis that green tea dietary polyphenols, by targeting SIRT1, can constitute an adjuvant strategy for counteracting the initial damage of the diabetic heart, before the occurrence of diabetic cardiomyopathy.

WIN Symposium 2022 - Abstract Poster Presentations.

WIN Symposium 2022 - Abstract Poster Presentations.

CircRNA and miRNA expression analysis in livers of mice with Toxoplasma gondii infection.

Toxoplasmosis is an important zoonotic parasitic disease caused by Toxoplasma gondii (T. gondii). However, the functions of circRNAs and miRNAs in response to T. gondii infection in the livers of mice at acute and chronic stages remain unknown. Here, high-throughput RNA sequencing was performed for detecting the expression of circRNAs and miRNAs in livers of mice infected with 20 T. gondii cysts at the acute and chronic stages, in order to understand the potential molecular mechanisms underlying hepatic toxoplasmosis. Overall, 265 and 97 differentially expressed (DE) circRNAs were found in livers at the acute and chronic infection stages in comparison with controls, respectively. In addition, 171 and 77 DEmiRNAs were found in livers at the acute and chronic infection stages, respectively. Functional annotation showed that some immunity-related Gene ontology terms, such as "positive regulation of cytokine production", "regulation of T cell activation", and "immune receptor activity", were enriched at the two infection stages. Moreover, the pathways "Valine, leucine, and isoleucine degradation", "Fatty acid metabolism", and "Glycine, serine, and threonine metabolism" were involved in liver disease. Remarkably, DEcircRNA 6:124519352|124575359 was significantly correlated with DEmiRNAs mmu-miR-146a-5p and mmu-miR-150-5p in the network that was associated with liver immunity and pathogenesis of disease. This study revealed that the expression profiling of circRNAs in the livers was changed after T. gondii infection, and improved our understanding of the transcriptomic landscape of hepatic toxoplasmosis in mice.

Gender Differences in microRNA Expressions as Related to Long-Term Graft Function in Kidney Transplant Patients.

In recent studies, much has been discussed about biomarkers used in the evaluation of the transplanted graft function. However, there remains a lack of research regarding the long-term effects of microRNAs (miRNAs) on the different genders for kidney transplant (KTx) patients. In this study, we aim to assess the functions of miRNAs on long term outcomes of KTx patients by extracting differently expressed miRNAs between patients of normal graft function and graft dysfunction, while further analyzing their impact on the different genders. We analyzed the data of 40 patients who had received KTx for a period of more than ten years and included data regarding renal function, immuno-related markers and plasma miRNAs. Data were classified by gender for further studies. Twelve out of 17 females and 8 out of 23 males had undergone graft dysfunction. Renal function analysis showed significantly worse outcomes in the female patients. There were five differently expressed miRNAs between the female control group and female dysfunction group: miR-128-3p, miR-21-5p, miR-150-5p, miR-92a-3p and miR-15a-5p, and five between the male control group and male dysfunction group: miR-23a-3p, miR-126-3p, miR-142-3p, miR-223-3p and miR-26a-5p. Gender differences exist in incidences of kidney graft dysfunction, with male patients displaying better preservation in graft functions. Overall, these differently expressed miRNAs either enhance or suppress host immune responses. They can be predictive markers for graft survival and can also be important factors that lead to worse long term kidney graft function in females when compared to males.

Genome-Wide Identification of miRNAs and Its Downstream Transcriptional Regulatory Network during Seed Maturation in Tilia tuan

Seed maturation not only determines the qualities and yields of seeds, but also affects seed storage and quality preservation. MicroRNAs (miRNAs) are a ubiquitous regulatory factor of gene expression in eukaryotes, which participate in the complex regulatory network of gene expression during seed maturation. However, miRNAs involved in maturation of Tilia tuan are still unknown. To reveal the role of miRNAs in T. tuan, small RNAs were profiled by high-throughput sequencing during seed maturation at five developmental stages. By predicting the target genes of miRNAs, the expression patterns of miRNAs during seed maturation were analyzed to identify those related to seed maturation. A total of 187 known miRNAs belonging to 42 miRNA families were found at five different seed maturation stages. Based on the analysis of unknown sequences, eight novel miRNAs were identified; 11,775 targets of 195 miRNAs were identified. Large numbers of miRNAs with diverse expression patterns, multiple-targeting and co-targeting of many miRNAs, and a complex regulatory network of miRNA-target genes were identified during seed maturation. These miRNAs and their targets may be involved in fatty acid, ABA, and lignin biosynthesis. Our study provides more information about the miRNA regulatory network and deepens our understanding of the function of miRNAs in T. tuan. miRNAs are revealed to be crucial during seed maturation, which provides a basis for further study of the regulatory role of miRNAs during seed maturation.