Identification of miR-1 and miR-499 in chronic atrial fibrillation by bioinformatics analysis and experimental validation.

Background: Atrial fibrillation (AF) is one of the most prevalent arrhythmias and is characterized by a high risk of heart failure and embolic stroke, yet its underlying mechanism is unclear. The primary goal of this study was to establish a miRNA-mRNA network and identify the miRNAs associated with chronic AF by bioinformatics and experimental validation. Methods: The GSE79768 dataset was collected from the Gene Expression Omnibus(GEO) database to extract data from patients with or without persistent AF. Differentially expressed genes (DEGs) were identified in left atrial appendages (LAAs). The STRING platform was utilized for protein-protein interaction (PPI) network analysis. The target miRNAs for the top 20 hub genes were predicted by using the miRTarBase Web tool. The miRNA-mRNA network was established and visualized using Cytoscape software. The key miRNAs selected for verification in the animal experiment were confirmed by miRwalk Web tool. We used a classic animal model of rapid ventricular pacing for chronic AF. Two groups of animals were included in the experiment, namely, the ventricular pacing group (VP group), where ventricular pacing was maintained at 240-280 bpm for 2 weeks, and the control group was the sham-operated group (SO group). Finally, we performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate the expression of miR-1 and miR-499 in LAA tissues of the VP group and the SO group. Left atrial fibrosis and apoptosis were evaluated by Masson staining and caspase-3 activity assays, respectively. Results: The networks showed 48 miRNAs in LAA tissues. MiR-1 and miR-499 were validated using an animal model of chronic AF. The expression level of miR-1 was increased, and miR-499 was decreased in VP group tissues compared to SO group tissues in LAAs (P < 0.05), which were correlated with left atrial fibrosis and apoptosis in AF. Conclusion: This study provides a better understanding of the alterations in miRNA-1 and miR-499 in chronic AF from the perspective of the miRNA-mRNA network and corroborates findings through experimental validation. These findings may offer novel potential therapeutic targets for AF in the future.

Evaluation of Left Ventricular Mass in Different Cardiac Geometry Using Three-Dimensional Contrast-Enhanced Echocardiography.

A total of 69 patients were enrolled in the study, including 23 patients with hypertrophic cardiomyopathy (HCM), 26 patients with Left Ventricle (LV) enlargement comprising 16 dilated cardiomyopathy (DCM) patients and 10 ischemic cardiomyopathy (ICM) patients, and 20 control subjects. All patients underwent 2DE, contrast-enhanced 2DE (Contrast-2DE), 3DE, Contrast-3DE, and single photon emission computed tomography (SPECT) examinations. The 2DE-AL and 3DE methods measured the left ventricular mass (LVM). The results were compared with those measured by SPECT. The measured LVM of the 69 patients was systematically overestimated by 2DE-AL (177.4 ± 56.2 g), Contrast-2DE-AL (174.5 ± 55.5 g), 3DE (167.3 ± 59.2 g), and Contrast-3DE (154.2 ± 46.7 g) when compared with SPECT (148.5 ± 52.4 g) (P < 0.05), while Contrast-3DE provided the best agreement with SPECT in LVM measurement (r = 0.898, P < 0.001) and had the smallest deviation (5.7 ± 23.1 g). 3DE overestimated LVM more compared to Contrast-3DE in LV hypertrophy group (165.5 ± 37.9 g versus 153.5 ± 27.6 g, P = 0.003) and LV enlargement group (204.5 ± 69.3 g versus 183.5 ± 53.5 g, P = 0.006). For 2DE methods, there was no significant difference between the LVM obtained with or without contrast enhancement in control group (132.3 ± 23.6 g versus 128.4 ± 23.3 g), LV hypertrophy group (177.7 ± 38.6 versus 178.3 ± 30.9 g, P = 0.889), and LV enlargement group (211.9 ± 63.2 g versus 206.5 ± 66.0 g, P = 0.386). The difference between LVM measured by 2DE-AL and SPECT was the greatest (27.9 ± 34.0 g), especially in LV hypertrophy group and LV enlargement group (LV hypertrophy group 39.7 ± 26.0 g; LV enlargement group 24.2 ± 42.8 g). To conclude, Contrast-3DE and SPECT show greater consistency in LVM measurement, especially in cardiomyopathy, when compared with 2DE. Administering contrast can effectively reduce the overestimation of LVM by non-contrast DE.

Resveratrol reliefs DEHP-induced defects during human decidualization.

Di-(2-Ethylhexyl) phthalate (DEHP) is widely used as an additive in many plastic products. Studies have revealed that DEHP persistent exposure can affect embryonic development and lead to adverse female reproductive disorders. The establishment of pregnancy involves extensive changes in the endometrial tissue, including massive extracellular matrix (ECM) remodeling. Decidualization of the endometrium provides a suitable environment for subsequent growth by causing changes in the morphology of the uterine stromal cells, is a key process in human pregnancy. Resveratrol (RSV) is a natural polyphenolic plant antitoxin with a wide range of pharmacological effects. Growing evidence indicates that RSV has therapeutic effects on certain female reproductive disorders. In this study, the effect of DEHP on cell viability was investigated by cell proliferation assay. Cell decidualization was induced in vitro, and the downregulation of molecules associated with decidualization was confirmed through quantitative real-time PCR and western blot analysis. Immunofluorescence analysis revealed alteration in cell morphology, and found that administration of DEHP sufficiently induced ERα entry into the nucleus. The effect of DEHP on cells was fully verified by RNA-seq analysis. Interestingly, an upregulation of decidual molecules was observed after rescue with RSV, which was confirmed by RNA-seq transcriptome analysis and quantitative real-time PCR assay. Additionally, the expression of ECM remodeling-related genes was significantly restored by RSV administration. The study revealed the potential mechanisms of DEHP-induced decidualization defects and the functional relieving roles of RSV while providing a perspective therapeutic candidate for alleviating the DEHP-induced deficiencies in decidualization.

Transcriptome analysis reveals a potential regulatory mechanism of the lnc-5423.6/IGFBP5 axis in the early stages of mouse thymic involution.

Age-related thymic involution is one of the significant reasons for induced immunity decline. Recent evidence has indicated that lncRNAs are widely involved in regulating organ development. However, the lncRNA expression profiles in mouse thymic involution have not been reported. In this study, we collect mouse thymus at the ages of 1 month, 3 months, and 6 months for sequencing to observe the lncRNA and gene expression profiles in the early stages of thymic involution. Through bioinformatics analysis, a triple regulatory network of lncRNA-miRNA-mRNA that contains 29 lncRNAs, 145 miRNAs and 12 mRNAs that may be related to thymic involution is identified. Among them, IGFBP5 can reduce the viability, inhibit proliferation and promote apoptosis of mouse medullary thymic epithelial cell line 1 (MTEC1) cells through the p53 signaling pathway. In addition, miR-193b-3p can alleviate MTEC1 cell apoptosis by targeting IGFBP5. Notably, lnc-5423.6 can act as a molecular sponge of miR-193b-3p to regulate the expression of IGFBP5. In summary, lnc-5423.6 enhances the expression of IGFBP5 by adsorption of miR-193b-3p, thereby promoting MTEC1 cell apoptosis.

Characterization of circular RNA expression profiles in the age-related thymic involution of Magang goose.

The thymus is a vital immune organ, but its function gradually declines with age. Circular RNAs (circRNAs) are related to the development of tissues and organs. In this study, bioinformatics analysis showed that 1329, 755, and 417 circRNAs were differentially expressed between the comparison groups of 6-month age (M6) and 20-embryo age (E20), 3-day post-hatch (P3), and 3-month age (M3) Magang geese, respectively. Among them, 167 circRNAs were differentially co-expressed between thymic development (E20, P3, and M3) and involution (M6). Functional analysis showed significant enrichment of phosphorylation and positive regulation of GTPase activity. Furthermore, pathway analysis has shown that glycerolipid metabolism and the Wnt signaling pathway are critical pathways in the thymic involution process. Finally, we constructed the competitive endogenous RNA (ceRNA) network. The results of this study suggest that circRNAs may be involved in the age-related thymic involution of the Magang goose.

Molecular Mechanism of Mouse Uterine Smooth Muscle Regulation on Embryo Implantation.

Myometrium plays critical roles in multiple processes such as embryo spacing through peristalsis during mouse implantation, indicating vital roles of smooth muscle in the successful establishment and quality of implantation. Actin, a key element of cytoskeleton structure, plays an important role in the movement and contraction of smooth muscle cells (SMCs). However, the function of peri-implantation uterine smooth muscle and the regulation mechanism of muscle tension are still unclear. This study focused on the molecular mechanism of actin assembly regulation on implantation in smooth muscle. Phalloidin is a highly selective bicyclic peptide used for staining actin filaments (also known as F-actin). Phalloidin staining showed that F-actin gradually weakened in the CD-1 mouse myometrium from day 1 to day 4 of early pregnancy. More than 3 mice were studied for each group. Jasplakinolide (Jasp) used to inhibit F-actin depolymerization promotes F-actin polymerization in SMCs during implantation window and consequently compromises embryo implantation quality. Transcriptome analysis following Jasp treatment in mouse uterine SMCs reveals significant molecular changes associated with actin assembly. Tagln is involved in the regulation of the cell cytoskeleton and promotes the polymerization of G-actin to F-actin. Our results show that Tagln expression is gradually reduced in mouse uterine myometrium from day 1 to 4 of pregnancy. Furthermore, progesterone inhibits the expression of Tagln through the progesterone receptor. Using siRNA to knock down Tagln in day 3 SMCs, we found that phalloidin staining is decreased, which confirms the critical role of Tagln in F-actin polymerization. In conclusion, our data suggested that decreases in actin assembly in uterine smooth muscle during early pregnancy is critical to optimal embryo implantation. Tagln, a key molecule involved in actin assembly, regulates embryo implantation by controlling F-actin aggregation before implantation, suggesting moderate uterine contractility is conducive to embryo implantation. This study provides new insights into how the mouse uterus increases its flexibility to accommodate implanting embryos in the early stage of pregnancy.

iTRAQ-based proteomic analysis of 17ß-Estradiol-induced anti-proliferation and apoptosis in mouse thymic epithelial cells by disturbing ribosomal biogenesis.

Many evidences have suggested that estrogen was associated with thymic atrophy and suppressed thymocyte functions. Thymic epithelial cells (TECs), as a crucial constituent of thymic stroma support a unique microenvironment for thymocyte maturation, but the effects of estrogen on TECs were poorly understood. In our study, we found that 17ß-Estradiol (17ß-E2), one of the primary estrogens, could significantly inhibit cell proliferation, and cause cell cycle arrest in G2/M phase and apoptosis in mouse thymic epithelial cell line 1 (MTEC1 cells) with time- and dose- dependent. Above all, we provided the systemic and sufficient proteomic profiling of 17ß-E2 (50 nmol/L) acting on MTEC1 cells through isobaric tags for relative and absolute quantitation and LC-MS/MS (Liquid Chromatography Mass Spectrometry/Mass Spectrometry). A total of 71 differentially expressed proteins were identified, of which 61 were up-regulated and 10 were down-regulated. Particularly, the differential expression of abundant ribosomal proteins (RPs) was drawing our attention, including RPL3, RPL4, RPS11, RPL17, RPL5, RPS9, RPL13, RPL23A, RPLP2, RPS15A, and RPL29. Most of these proteins have been widely reported exerting extra-ribosomal function associated with the proliferation and apoptosis of distinct cell types, but not yet observed in TECs. Moreover, bioinformatics analysis revealed that disturbance of ribosomal biogenesis was closely related to the anti-proliferation and apoptosis in MTEC1 cells upon 17ß-E2. These data highlighted the possible mechanisms of 17ß-E2 on MTEC1 cells through showing adequate differential protein expression profiles. We inferred that 17ß-E2 induced anti-proliferation and apoptosis in MTEC1 cells in response to alterations of ribosome biogenesis and RPs expression, which will contribute to gaining insight into the internal mechanism of thymic degeneration and exploiting to treat autoimmune diseases in the future.

Effects of PAMK on lncRNA, miRNA, and mRNA expression profiles of thymic epithelial cells.

Polysaccharides from Atractylodes macrocephala Koidz (PAMK) can promote the proliferation of thymocytes and improve the body's immunity. However, the effect of PAMK on thymic epithelial cells has not been reported. Studies have shown that miRNAs and lncRNAs are key factors in regulating cell proliferation. In this study, we found that PAMK could promote the proliferation of mouse medullary thymic epithelial cell line 1 (MTEC1) cells through CCK-8 and EdU experiments. To further explore its mechanism, we detected the effect of PAMK on the expression profiles of lncRNAs, miRNAs, and mRNAs in MTEC1 cells. The results showed that PAMK significantly affected the expression of 225 lncRNAs, 29 miRNAs, and 800 mRNAs. Functional analysis showed that these differentially expressed genes were significantly enriched in cell cycle, cell division, NF-kappaB signaling, apoptotic process, and MAPK signaling pathway. Finally, we used Cytoscape to visualize lncRNA-miRNA-mRNA(14 lncRNAs, 17 miRNAs, 171 mRNAs) networks based on ceRNA theory. These results suggest that lncRNAs and miRNAs may be involved in the effect of PAMK on the proliferation of MTEC1 cells, providing a new research direction for exploring the molecular mechanism of PAMK promoting the proliferation of thymic epithelial cells.

miR-152-3p Represses the Proliferation of the Thymic Epithelial Cells by Targeting Smad2.

MicroRNAs (miRNAs) control the proliferation of thymic epithelial cells (TECs) for thymic involution. Previous studies have shown that expression levels of miR-152-3p were significantly increased in the thymus and TECs during the involution of the mouse thymus. However, the possible function and potential molecular mechanism of miR-152-3p remains unclear. This study identified that the overexpression of miR-152-3p can inhibit, while the inhibition of miR-152-3p can promote, the proliferation of murine medullary thymic epithelial cell line 1 (MTEC1) cells. Moreover, miR-152-3p expression was quantitatively analyzed to negatively regulate Smad2, and the Smad2 gene was found to be a direct target of miR-152-3p, using the luciferase reporter assay. Importantly, silencing Smad2 was found to block the G1 phase of cells and inhibit the cell cycle, which was consistent with the overexpression of miR-152-3p. Furthermore, co-transfection studies of siRNA-Smad2 (siSmad2) and the miR-152-3p mimic further established that miR-152-3p inhibited the proliferation of MTEC1 cells by targeting Smad2 and reducing the expression of Smad2. Taken together, this study proved miR-152-3p to be an important molecule that regulates the proliferation of TECs and therefore provides a new reference for delaying thymus involution and thymus regeneration.

Proteomic analysis of zearalenone toxicity on mouse thymic epithelial cells.

Zearalenone (ZEA) is one of the most major food contaminants in cereal crops worldwide, risking health of both livestock and humans. This study aimed to assess the cytotoxicity and the underlying mechanism of ZEA on thymic epithelial cells. By using proteomics analysis, we identified 596 differentially expressed proteins in MTEC1 cells upon zearalenone exposure, of which 245 were upregulated and 351 were downregulated. Gene ontology (GO) analysis suggested that differentially expressed proteins were participated in protein synthesis, oxidative phosphorylation, and ATP binding. KEGG pathway enrichment analysis showed that differentially expressed proteins were mainly related to mitochndrial metabolism, such as citrate cycle (TCA cycle) and oxidative phosphorylation. We demonstrated that ZEA treatment was able to increase the intracellular reactive oxygen species (ROS) level, to decrease ΔΨm, ATP level, and the copy number of mtDNA, leading to necrotic cell death. Moreover, we showed that ZEA treatment inhibited cell proliferation and induced G2/M phase arrest by downregulation of proliferation-associated proteins ERK, p-ERK, CDK1, and p-CHK1. Taken together, we found that the toxicity of ZEA on thymic epithelial cells is mainly caused by the inhibition of mitochondrial dysfunction and cell proliferation. Our study might open new avenues for treatment strategies.

miR-199b-5p enhances the proliferation of medullary thymic epithelial cells via regulating Wnt signaling by targeting Fzd6.

Thymic epithelial cells (TECs) are essential regulators of T-cell development and selection. miRNAs play critical roles in regulating TEC proliferation during the process of thymic aging. Our previous studies revealed that miR-199b-5p was upregulated in TECs from 1- to 3-month-old mice. But its function and potential mechanism are not clear. We hypothesized that miR-199b-5p may play an important role in age-related thymus involution via targeting some genes. To confirm it, the murine thymic epithelial cell line 1 (MTEC1) cells were used. Our results showed that overexpression of miR-199b-5p can enhance MTEC1 cell proliferation. On the contrary, repression of miR-199b-5p can inhibit MTEC1 cell proliferation. Meanwhile, it was confirmed that frizzled receptor 6 (Fzd6) is the direct target gene of miR-199b-5p. Furthermore, overexpression of miR-199b-5p can upregulate the expressions of ß-catenin, Tcf7, Wnt4, and C-myc to activate Wnt signaling and cell cycle signaling. Silence of Fzd6 and co-transfection with siFzd6 and miR-199b-5p mimic/inhibitor confirmed that the biological function of miR-199b-5p is indeed by targeting Fzd6 in medullary TECs. Overall, miR-199b-5p is an important regulator in medullary TEC proliferation through targeting Fzd6 to activate Wnt signaling and cell cycle signaling. Our data indicate that miR-199b-5p may block the process of thymic aging and be a potential therapeutic target for thymus involution.

Comprehensive analysis of lncRNAs, miRNAs and mRNAs related to thymic development and involution in goose.

Thymic involution is a sign of immunosenescence, but little is known about it in goose. miRNAs and lncRNAs are critical factors regulating organ growth and development. In this study, we comprehensively analyzed the profiles of lncRNAs, miRNAs and mRNAs during the development and involution of the thymus in Magang goose. The results showed that 2436 genes, 16 miRNAs and 417 lncRNAs were differentially co-expressed between the developmental (20-embryo age, 3-day post-hatch and 3-month age) and degenerative (6-month age) stages. The functional analysis showed that these differentially expressed genes were significantly enriched in cell proliferation, cell adhesion, apoptotic signaling pathway, and Notch signaling pathway. In addition, we established a gene-gene network through the STRING database and identified 50 key genes. Finally, we constructed a miRNA-mRNA network followed by a lncRNA-miRNA-mRNA network. These results suggest that lncRNAs and miRNAs may be involved in the regulation of thymic development and involution in goose.

Resveratrol alleviates zea-induced decidualization disturbance in human endometrial stromal cells.

Decidualization, which endows the endometrium competency to adopt developing embryo and maintain appropriate milieu for following growth, is a pivotal process for human pregnancy. The delicate collaboration between ovarian steroid hormones estrogen and progesterone governs the process of decidualization and subsequent establishment of embryo implantation. Mycotoxin zearalenone (ZEA) is well known as endocrine disruptor due to its potent estrogenic activity. In this study, we investigated effects of ZEA on decidualization of human endometrial stromal cells. Results indicated that ZEA exhibited its inhibitory action through nuclear translocation of ERα. ZEA exposure led to dampened progress of decidualization, which could be attenuated by estrogen receptor antagonist. Notably, resveratrol (RSV) administration restored impaired decidualization process by induction of anti-oxidative gene glutathione peroxidase 3 (GPX3). This study provides novel insights into the mechanism underlying adverse effects of ZEA in human decidual stromal cells and suggests RSV a potential therapeutic candidate to alleviate ZEA-induced cytotoxicity during decidualization.

Prognostic value of pulmonary oedema assessed by lung ultrasound in patient with acute heart failure.

It is very important to assess pulmonary oedema in patients with acute heart failure. The aim of the study was to investigate the accuracy of lung ultrasound in evaluating pulmonary oedema and to explore lung ultrasound in predicting the prognosis. One hundred twenty-four acute heart failure patients were divided into 3 groups, according to the total number of lung ultrasound B-lines groups: B-lines < 15 was the mild pulmonary oedema group (33 cases), 15 ≤ B-lines < 30 was the moderate pulmonary oedema group (33 cases), and B-lines ≥ 30 was the severe pulmonary oedema group (58 cases). The PiCCO monitoring system was used in 11 patients and measured 26 times in different clinical situations. EVLWI have a higher positive correlation with B-lines (r = 0.95), compared with NT-proBNP and E/e' (r = 0.72, r = 0.62). During 1 year of follow-up, a multivariate cox regression analysis showed that age, E/e' and B-lines ≥ 30 at admission (C-index of 75%) were risk factors for prognosis. 12-month event-free survival showed a significantly worse outcome was observed in patients with ≥ 30 B-lines at admission. B-lines have a good correlation with EVLWI; age, E/e' and B-lines ≥ 30 at admission were risk factors for prognosis.

miR-205-5p inhibits thymic epithelial cell proliferation via FA2H-TFAP2A feedback regulation in age-associated thymus involution.

Thymic epithelial cells (TECs) are essential regulators of T cell development and selection. microRNAs (miRNAs) play critical roles in regulating TECs proliferation during thymus involution. miR-205-5p is highly expressed in TECs and increases with age. However, the function and potential mechanism of miR-205-5p in TECs are not clear. miRNA expression was profiled using TECs from male and female mice at 1 and 3 months old. A total of 325 differentially expressed miRNAs (DEMs) were detected at different ages in two sexes. 24 of the DEMs had the same trend between males and females. Among them, miR-205-5p had the highest fold change. Our results showed that the expression of miR-205-5p was dramatically increased in TECs from 1 to 9 months old mice. miR-205-5p mimic inhibited TECs proliferation. Moreover, we confirmed that Fa2h was the direct target gene of miR-205-5p and FA2H was significantly decreased in TECs with increased expression of miR-205-5p. Silencing of Fa2h inhibited TECs proliferation. Furthermore, we found that the expression of Tfap2a could be promoted by FA2H and that TFAP2A could interact with miR-205-5p in TECs. Overall, miR-205-5p is an important regulator of TECs proliferation and regulates age-associated thymus involution via the miR-205-5p-FA2H-TFAP2A feedback regulatory circuit. miR-205-5p might act as a potential biomarker in TECs for age-related thymus involution.

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus.

Thymic degeneration and regeneration are regulated by estrogen and androgen. Recent studies have found that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in organ development. In this study, RNA sequencing (RNA-seq) results showed that ovariectomy significantly affected 333 lncRNAs, 51 miRNAs, and 144 mRNAs levels (p < 0.05 and |log2fold change| > 1), and orchiectomy significantly affected 165 lncRNAs, 165 miRNAs, and 208 mRNA levels in the thymus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) were closely related to cell development and immunity. Next, we constructed two lncRNA-miRNA-mRNA networks using Cytoscape based on the targeting relationship between differentially expressed miRNAs (DEMs) and DEGs and differentially expressed lncRNAs (DELs) analyzed by TargetScan and miRanda. Besides, we screened DEGs that were significantly enriched in GO and in ceRNA networks to verify their expression in thymocytes and thymic epithelial cells (TECs). In addition, we analyzed the promoter sequences of DEGs, and identified 25 causal transcription factors. Finally, we constructed transcription factor-miRNA-joint target gene networks. In conclusion, this study reveals the effects of estrogen and androgen on the expression of miRNAs, lncRNAs, and mRNAs in mice thymus, providing new insights into the regulation of thymic development by gonadal hormones and non-coding RNAs.

Profiling analysis of 17ß-estradiol-regulated lncRNAs in mouse thymic epithelial cells.

Thymus is the primary organ for T cell differentiation and maturation. Many studies have demonstrated that estrogen plays a crucial role in thymic epithelial cell (TEC) proliferation during thymic involution. LncRNAs are involved in various biological processes; however, estrogen-mediated lncRNA expression in TECs has not been yet reported. To address this question, the mouse medullary thymic epithelial cell line 1 (MTEC1) was treated with 17ß-estradiol (E2). By using CCK8 assay and flow cytometry, we found that E2 was able to inhibit viability and proliferation of MTEC1 cells. The expression profiles of lncRNAs in MTEC1 cells with or without E2 treatment were then measured by RNA-Seq, and a total of 962 lncRNAs and 2,469 mRNAs were shown to be differentially expressed. The reliability of RNA-Seq was confirmed by quantitative RT-PCR. Correlation analysis was conducted to investigate the potential function of lncRNAs. According to gene ontology (GO) analysis, differentially expressed lncRNAs were mainly related to cell proliferation, cell cycle and cell apoptosis. KEGG pathway analysis indicated that these lncRNAs were associated with several pathways, namely immunological activity, metabolism and cytokine-cytokine receptor interaction. In conclusion, our study provided a novel direction for studying the relationship between lncRNAs and E2 in the thymus.

Transcriptional profiling analysis of Zearalenone-induced inhibition proliferation on mouse thymic epithelial cell line 1.

Zearalenone (ZEA) was a mycotoxin biosynthesized by a variety of Fusarium fungi via a polypeptide pathway. ZEA has significant toxic reaction on immune cells. Thymic epithelial cells (TECs) as a crucial constituent of thymic stroma can provide unique microenvironment for thymocyte maturation, but the mechanism of ZEA affecting the TECs is poorly understood. The basic data about gene expression differences for the ZEA on thymic epithelial cell line 1 (MTEC1) will help us to elucidate this mechanism. Here, cell viability and proliferation assay and transcriptome sequencing on MTEC1 treated with ZEA were performed. 4188 differentially expressed genes (DEGs) between ZEA treated and control groups were identified, confirmed and analyzed. Our results showed that 10-50µg/ml ZEA significantly inhibited MTEC1 proliferation and arrested cell cycle at G2/M phase. Gene ontology and KEGG pathway analysis revealed that Chemokine, JAK-STAT and Toll-like receptor signaling pathway, were involved in the cell cycle pathway. 16 key genes involved in the cell cycle processes were validated and the results suggested that Mitotic catastrophe (MC) may take part in ZEA inhibition of METC1 cell proliferation. These data highlighted the importance of cell cycle pathway in MTEC1 treated with ZEA, and will contribute to get the molecular mechanisms of ZEA inhibition of MTEC1 cell proliferation.