scholarly journals SAT-455 Mouse Thyroid Responds to Iodine Overload by Transcriptionally Enhancing the Keap1/Nrf2 Antioxidant Response and by Upregulating Nrf2-Dependent and Independent Inflammatory and Fibrosis Pathways

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dionysios V Chartoumpekis ◽  
Panos Ziros ◽  
Ioannis Habeos ◽  
Venetsana Kyriazopoulou ◽  
Adam Smith ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Sodium Iodide ◽  
Target Genes ◽  
Rna Extraction ◽  
Xenobiotic Metabolism ◽  
Antioxidant Response ◽  
Differentially Expressed ◽  
P Value ◽  
Rna Seq ◽  
Thyroid Cells

Abstract Nrf2 (Nfe2l2) is a transcription factor that regulates a series of cytoprotective and antioxidant enzymes. Its cytoplasmic inhibitor Keap1 senses the presence of oxidative or electrophilic stress though the interaction of sulfhydryl groups of its cysteines with reactive species and ceases to bind Nrf2. Thus, Nrf2 can transfer to the nucleus and induce its target genes. Follicular thyroid cells have physiologically high levels of reactive oxygen species as oxidation of iodine is essential for iodination of thyroglobulin and thyroid hormones synthesis. We have shown previously that Nrf2 pathway is active in thyroid and regulates the transcription of thyroglobulin. We thus hypothesized that the response of thyroid to iodine excess should comprise Nrf2-dependent and -independent pathways. To this end, 3 months-old male C57Bl6J WT or Nrf2 knockout (KO) mice were exposed to 0.05% sodium iodide in their water for 7 days. Thyroids were excised and used for RNA extraction; RNA-seq was performed by Exiqon, with a fold-change cutoff set at 2. Selected representative genes of the enriched pathways were quantified by real-time qPCR to validate RNA-seq results. Pathway analysis of the differentially expressed genes was performed using the Ingenuity Pathway Analysis (IPA) software. Pathways that were enriched with a p-value<0.05 were considered significant. 828 genes were differentially expressed in response to iodine exposure; 66% were upregulated, as were most of the highly enriched pathways (related to inflammatory-immune response, antioxidant response, xenobiotic metabolism, platelet activation and calcium signaling). About 300 genes were differentially expressed between WT and KO mice; highly enriched pathways were related to glutathione and xenobiotic metabolism, Ahr signaling and Nrf2 signaling and were all downregulated in KO mice. Analysis of the potential upstream regulators of these highly enriched pathways revealed that Nrf2 and NfkB are major regulators of the antioxidant and inflammatory response induction upon iodine exposure and that Tgfβ-Smad cascade regulates the induction of fibrosis signaling. Last, we performed an analysis limited to already known thyroid pathways. A few genes were enriched following this method; upregulation of Duoxa1 (hydrogen peroxide generator) and downregulation of Nis (sodium iodide symporter) upon iodine exposure, which are expected responses, and the downregulation of thyroglobulin and upregulation of Duoxa1 in KO mice that confirm our previous findings. In conclusion, Nrf2-driven cytoprotective response is upregulated after iodine overload along with induction of inflammatory pathways. Nrf2 regulates transcriptomic responses in the thyroid, including a small but significant part of the response to iodine challenge. Hence, Nrf2 can be considered a novel player in the frontiers of thyroid antioxidant response and thyroid economy.

scholarly journals RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma

2020 ◽  
Author(s):  
Li-rong Yan ◽  
Ang Wang ◽  
Qian Xu ◽  
Ben-gang Wang
Keyword(s):  
Signaling Pathway ◽  
High Throughput ◽  
Target Genes ◽  
Expression Profiles ◽  
Biological Effects ◽  
Differentially Expressed ◽  
P Value ◽  
Hippo Signaling ◽  
Rna Seq ◽  
Normal Tissues

Abstract Background: Recently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNA may regulate the progression of a variety of tumors, and tsRNA is expected to become a new diagnostic marker of cancer. However, the expression of tsRNA is obscure and should be elucidated in CCA.Methods: We collected CCA tissues and adjacent normal tissues from three patients. High-throughput RNA-seq was utilized to determine the overall expression profiles of tsRNA in CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The biological effects and potential signaling pathways of dysregulated tsRNAs between the CCA and adjacent normal tissues were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.Results: High-throughput RNA-seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated and 294 tsRNAs were downregulated in CCA compared with adjacent normal tissues (|log2 (fold change)| >=1 and p value< 0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, tRF-39-0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, and cAMP signaling pathway and in growth hormone synthesis, secretion and action.Conclusion: Differentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the progression of CCA.

scholarly journals Gene Expression and Alternative Splicing Datasets Analyses of MDS with Ring Sideroblasts Highlight Alternative Branchpoint Usage in Genes Involved in Iron Metabolism and Erythropoiesis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1972-1972
Author(s):  
Abderrahmane Bousta ◽  
Sabrina Bondu ◽  
Alexandre Houy ◽  
Nicolas Cagnard ◽  
Carine Lefevre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Iron Metabolism ◽  
Target Genes ◽  
Differentially Expressed ◽  
P Value ◽  
Rna Seq ◽  
Splice Sites ◽  
Gene Sets ◽  
Ring Sideroblasts

Abstract Introduction SF3B1 hotspot mutations are associated with various cancers like uveal melanoma, chronic lymphocytic leukemia and myelodysplastic syndrome with ring sideroblasts (MDS-RS). These mutations affect RNA splicing by the use of alternative branchpoints resulting in an aberrant 3' splice site (ss) selection. RNA-sequencing (RNA-seq) analyzed to quantify exon-exon junctions identified aberrantly spliced transcripts in target genes, and half of them are predicted to be degraded by non-sense mediated decay. For this reason, target genes in SF3B1-mutated MDS remain partially characterized. In the present study, we performed deep RNA-seq analysis of bone marrow mononuclear cells in low/int-1 MDS with SF3B1 mutations to identify aberrant/cryptic splicing events among up or down-regulated gene sets. Methods SF3B1 MUT MDS (n=21) were compared to 6 SF3B1WT cases and 5 controls. Analysis of RNA-seq read count was performed using the Voom method associated with the Limma empirical Bayes analysis pipeline (https://genomebiology.biomedcentral.com/articles/10.1186/gb-2014-15-2-r29). Up or downregulated gene sets were identified using Gene Set Enrichment Analysis (GSEA, false discovery rate<0.1). Gene expression profiling data (Affymetrix Hu2.0) were also available for 26/27 patient samples. TopHat (v2.0.6) was used to align the reads against the human reference genome Hg19 RefSeq (RNA sequences, GRCh37) downloaded from the UCSC Genome Browser (http://genome.ucsc.edu). Read counts for splicing junctions from junctions.bed TopHat output were considered for a differential analysis using DESeq2. Only alternative acceptor splice sites (two or more 3′ss with junctions to the same 5′ss) and alternative donor splice sites (two or more 5′ss with junctions to the same 3′ss) with P-values ≤10−5 (Benjamini-Hochberg) and absolute Log2 (fold change) ≥1 were considered. Results Principal component analysis (PCA) nicely discriminated controls from patients, and patients according to the presence of a SF3B1 mutation. A set of 6971 genes was differently expressed (P- value<0.05) between SF3B1MUT and SF3B1WT cases and allows unsupervised clustering in two separated groups (Fig. 1). Distinct gene sets also discriminated SF3B1MUT or SF3B1WT from controls. Consistent with increased amount of erythroblasts in MDS-RS bone marrows, a set of erythroid genes including several genes involved in hemebiosynthesis pathway (ALAD, UROS, ALAS2, UROD) was significantly enriched in SF3B1MUT samples. Genes selected for their involvement in the core iron-sulfur cluster mitochondrial machinery (FXN, BOLA3, FDXR, GLRX5, ISCA2, NFS1, ISCU), the iron binding and trafficking (SLC25A38, ABCB10, TFR2, SLC25A37, ABCB6, FAM132B, SLC25A39, FTH1) and the cellular iron homeostasis (ACO1, ACO2, GLRX3) were also significantly enriched (FDR<10% and nominal P-value<0.05) when input in GSEA. Moreover, other enriched gene sets were G2M checkpoint, MYC targets, oxidative phosphorylation and E2F targets. All of these observations were similarly obtained when analyzing Affymetrix data. Furthermore SF3B1MUT samples with a K700E substitution harbored a specific pattern of deregulated genes, which allowed the ordering of SF3B1MUT samples according to the type of substitution. As previously reported by AlsafadiS et al (2016), analysis of splice junctions using DESeq2 revealed an overall high level of differences between SF3B1MUT and SF3B1WTsamples. Among more than 540 differentially spliced junctions, more than 80% involved an aberrant acceptor (3'ss) site. As determined by PCA, the top 50 genes associated with relevant aberrant junctions were linked to iron metabolism or erythropoiesis and differentially expressed between SF3B1MUT and SF3B1WTsamples. Conclusion In this study, we combined robust analyses of gene expression and aberrantly spliced transcript expression in MDS with SF3B1 mutation. By comparing SF3B1MUTversus SF3B1WT samples, we identified a set of deregulated genes in which both normally and aberrantly spliced transcripts were detected that could contribute to the physiopathology of MDS-RS. Figure 1 Hierarchical clustering and heatmapshowing differentially expressed genes (P-value<0.05) between SF3B1MUT (n=21, black) and SF3B1WT samples (n=6, grey) Ref. Alsafadi S et al. Nat Commun. 2016 Feb 4;7:10615. Figure 1. Hierarchical clustering and heatmapshowing differentially expressed genes (P-value<0.05) between SF3B1MUT (n=21, black) and SF3B1WT samples (n=6, grey) Ref. Alsafadi S et al. Nat Commun. 2016 Feb 4;7:10615. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comprehensive Analysis of lncRNAs and circRNAs Reveals the Metabolic Specialization in Oxidative and Glycolytic Skeletal Muscles

2019 ◽  
Vol 20 (12) ◽  
pp. 2855 ◽  
Author(s):  
Linyuan Shen ◽  
Mailin Gan ◽  
Qianzi Tang ◽  
Guoqing Tang ◽  
Yanzhi Jiang ◽  
...  
Keyword(s):  
Meat Quality ◽  
Skeletal Muscles ◽  
Target Genes ◽  
Fiber Type ◽  
Muscle Metabolism ◽  
Reduction Process ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Oxidation Reduction ◽  
Regulatory Analysis

The biochemical and functional differences between oxidative and glycolytic muscles could affect human muscle health and animal meat quality. However, present understanding of the epigenetic regulation with respect to lncRNAs and circRNAs is rudimentary. Here, porcine oxidative and glycolytic skeletal muscles, which were at the growth curve inflection point, were sampled to survey variant global expression of lncRNAs and circRNAs using RNA-seq. A total of 4046 lncRNAs were identified, including 911 differentially expressed lncRNAs (p < 0.05). The cis-regulatory analysis identified target genes that were enriched for specific GO terms and pathways (p < 0.05), including the oxidation-reduction process, glycolytic process, and fatty acid metabolic. All these were closely related to different phenotypes between oxidative and glycolytic muscles. Additionally, 810 circRNAs were identified, of which 137 were differentially expressed (p < 0.05). Interestingly, some circRNA-miRNA-mRNA networks were found, which were closely linked to muscle fiber-type switching and mitochondria biogenesis in muscles. Furthermore, 44.69%, 39.19%, and 54.01% of differentially expressed mRNAs, lncRNAs, and circRNAs respectively were significantly enriched in pig quantitative trait loci (QTL) regions for growth and meat quality traits. This study reveals a mass of candidate lncRNAs and circRNAs involved in muscle physiological functions, which may improve understanding of muscle metabolism and development from an epigenetic perspective.

scholarly journals Small RNA sequencing evaluation of renal microRNA biomarkers in dogs with X-linked hereditary nephropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Candice P. Chu ◽  
Shiguang Liu ◽  
Wenping Song ◽  
Ethan Y. Xu ◽  
Mary B. Nabity
Keyword(s):  
Small Rna ◽  
Target Genes ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Ckd Progression ◽  
Critical Pathways ◽  
Qrt Pcr ◽  
Hereditary Nephropathy ◽  
Differentially Expressed Mirnas

AbstractDogs with X-linked hereditary nephropathy (XLHN) are an animal model for Alport syndrome in humans and progressive chronic kidney disease (CKD). Using mRNA sequencing (mRNA-seq), we have characterized the gene expression profile affecting the progression of XLHN; however, the microRNA (miRNA, miR) expression remains unknown. With small RNA-seq and quantitative RT-PCR (qRT-PCR), we used 3 small RNA-seq analysis tools (QIAGEN OmicSoft Studio, miRDeep2, and CPSS 2.0) to profile differentially expressed renal miRNAs, top-ranked miRNA target genes, and enriched biological processes and pathways in CKD progression. Twenty-three kidney biopsies were collected from 5 dogs with XLHN and 4 age-matched, unaffected littermates at 3 clinical time points (T1: onset of proteinuria, T2: onset of azotemia, and T3: advanced azotemia). We identified up to 23 differentially expressed miRNAs at each clinical time point. Five miRNAs (miR-21, miR-146b, miR-802, miR-142, miR-147) were consistently upregulated in affected dogs. We identified miR-186 and miR-26b as effective reference miRNAs for qRT-PCR. This study applied small RNA-seq to identify differentially expressed miRNAs that might regulate critical pathways contributing to CKD progression in dogs with XLHN.

scholarly journals Bioinformatic Analysis of Circular RNA-Associated ceRNA Network Associated with Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiacheng Wu ◽  
Shui Liu ◽  
Yien Xiang ◽  
Xianzhi Qu ◽  
Yingjun Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Pathway Analysis ◽  
Target Genes ◽  
Kegg Pathway ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Kegg Pathway Analysis

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

scholarly journals Identification of Differentially Expressed MicroRNAs and Their Potential Target Genes in Adipose Tissue from Pigs with Highly Divergent Backfat Thickness

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 624
Author(s):  
Kai Xing ◽  
Xitong Zhao ◽  
Yibing Liu ◽  
Fengxia Zhang ◽  
Zhen Tan ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Patterns ◽  
Fat Deposition ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Backfat Thickness ◽  
P Value ◽  
Sibling Pairs ◽  
Differentially Expressed Mirnas

Fatty traits are very important in pig production. However, the role of microRNAs (miRNAs) in fat deposition is not clearly understood. In this study, we compared adipose miRNAs from three full-sibling pairs of female Landrace pigs, with high and low backfat thickness, to investigate the associated regulatory network. We obtained an average of 17.29 million raw reads from six libraries, 62.27% of which mapped to the pig reference genome. A total of 318 pig miRNAs were detected among the samples. Among them, 18 miRNAs were differentially expressed (p-value < 0.05, |log2fold change| ≥ 1) between the high and low backfat groups; 6 were up-regulated and 12 were down-regulated. Functional enrichment of the predicted target genes of the differentially expressed miRNAs, indicated that these miRNAs were involved mainly in lipid and carbohydrate metabolism, and glycan biosynthesis and metabolism. Comprehensive analysis of the mRNA and miRNA transcriptomes revealed possible regulatory relationships for fat deposition. Negatively correlated mRNA–miRNA pairs included miR-137–PPARGC1A, miR-141–FASN, and miR-122-5p–PKM, indicating these interactions may be key regulators of fat deposition. Our findings provide important insights into miRNA expression patterns in the backfat tissue of pig and new insights into the regulatory mechanisms of fat deposition in pig.

scholarly journals RNA-Seq Reveals the Expression Profiles of Long Non-Coding RNAs in Lactating Mammary Gland from Two Sheep Breeds with Divergent Milk Phenotype

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1565
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jiang Hu ◽  
Xiu Liu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Signaling Pathway ◽  
Target Genes ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are a kind of non-coding RNA with >200 nucleotides in length. Some lncRNAs have been proven to have clear regulatory functions in many biological processes of mammals. However, there have been no reports on the roles of lncRNAs in ovine mammary gland tissues. In the study, the expression profiles of lncRNAs were studied using RNA-Seq in mammary gland tissues from lactating Small-Tailed Han (STH) ewes and Gansu Alpine Merino (GAM) ewes with different milk yield and ingredients. A total of 1894 lncRNAs were found to be expressed. Compared with the GAM ewes, the expression levels of 31 lncRNAs were significantly up-regulated in the mammary gland tissues of STH ewes, while 37 lncRNAs were remarkably down-regulated. Gene Ontogeny (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the target genes of differentially expressed lncRNAs were enriched in the development and proliferation of mammary epithelial cells, morphogenesis of mammary gland, ErbB signaling pathway, and Wnt signaling pathway. Some miRNA sponges of differentially expressed lncRNAs, reported to be associated with lactation and mammary gland morphogenesis, were found in a lncRNA-miRNA network. This study reveals comprehensive lncRNAs expression profiles in ovine mammary gland tissues, thereby providing a further understanding of the functions of lncRNAs in the lactation and mammary gland development of sheep.

Analysis of the miRNA transcriptome during testicular development and spermatogenesis of the Mongolian horse

2020 ◽  
Vol 32 (6) ◽  
pp. 582
Author(s):  
Bei Li ◽  
Xiaolong He ◽  
Yiping Zhao ◽  
Dongyi Bai ◽  
Dandan Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Mammalian Species ◽  
Mature Mirnas ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
P Value ◽  
Testicular Development ◽  
Interaction Sites ◽  
Mongolian Horse

Numerous studies have shown that microRNAs (miRNAs) are essential for testicular development and spermatogenesis. In order to further characterise these physiological processes, three immature and three mature testes of the Mongolian horse were collected and six libraries were established. Using small RNA sequencing technology, 531 mature miRNAs were identified, including 46 novel miRNAs without previously ascribed functions. Among the 531 miRNAs, 421 were expressed in both immature and mature libraries, 65 miRNAs were found solely in immature testis libraries and 45 miRNAs were found solely in mature testis libraries. Furthermore, among the miRNAs that were identified in both immature and mature libraries, 107 were significantly differentially expressed (corrected P value (padj)&lt;0.05). Among the miRNAs that were only expressed in immature testes, two miRNAs were differentially expressed, whereas among the miRNAs that were only expressed in mature testes, nine miRNAs were differentially expressed. Comprehensive analysis of miRNA and mRNA expression profiles predicted 107 miRNA–mRNA interaction sites. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis of the predicted target genes suggested roles of the differentially expressed miRNAs in testicular development and spermatogenesis. These findings identify miRNAs as key factors in the development of the testes and spermatogenesis in the Mongolian horse, which may also help us to understand the mechanisms of fertility in related mammalian species.

scholarly journals Genome-wide Expression Profiling and Pathway Analysis in Cyclic Stretched Human Trabecular Meshwork Cells

2018 ◽  
Author(s):  
Michelle D. Drewry ◽  
Jingwen Cai ◽  
Inas Helwa ◽  
Eric Hu ◽  
Sabrina Liu ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Pathway Analysis ◽  
Trabecular Meshwork ◽  
Target Genes ◽  
Mechanical Stretch ◽  
Differentially Expressed ◽  
Receptor Protein ◽  
Trabecular Meshwork Cells ◽  
Differentially Expressed Mirnas ◽  
Significant Enrichment

AbstractPurposeRegulation of intraocular pressure is dependent upon homeostatic responses of trabecular meshwork (TM) cells to mechanical stretch. Despite the important roles of miRNAs in regulating TM function and aqueous outflow, it remains unclear how miRNA and their target genes interact in response to physiological cyclic mechanical stretch. We aimed to identify differentially expressed miRNAs and their potential targets in human TM cells in response to cyclic mechanical stress.MethodsMonolayers of TM cells from non-glaucomatous donors (n=3-6) were cultured in the presence or absence of 15% mechanical stretch, 1 cycle/s, for 6 or 24-hours using computer-controlled Flexcell Unit. We profiled the expression of 800 miRNAs using NanoString Human miRNA assays and identified differentially expressed miRNAs using the Bioconductor Limma package. We identified differentially expressed genes using Operon Human Oligo Arrays with GeneSpring software. Pathway analysis with WebGestalt identified stretch-related pathways. We used Integrative miRNA Target Finder from Ingenuity Pathway Analysis to identify potential miRNA-mRNA regulations.ResultsWe identified 540 unique genes and 74 miRNAs with differential expression in TM cells upon cyclic mechanical stretch. Pathway analysis indicated the significant enrichment of genes involved in Wnt-signaling, receptor protein serine/threonine kinase signaling, TGF-β pathway, and response to unfolded protein. We also identified several miRNA master regulators, including miR-19b-3p and miR-93-5p, which may act as switches to control several mechano-responsive genes.ConclusionsThis study suggests that cyclic mechanical stress of TM cells triggers alterations in the expression of both mRNAs and miRNAs implicated in glaucoma-associated pathways.

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