scholarly journals Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation

2022 ◽  
Vol 9 ◽  
Author(s):  
Carlos Garcia-Padilla ◽  
Angel Dueñas ◽  
Diego Franco ◽  
Virginio Garcia-Lopez ◽  
Amelia Aranega ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Target Genes ◽  
Hox Genes ◽  
Cardiac Development ◽  
Expression Profiles ◽  
Primitive Streak ◽  
Sinus Venosus ◽  
Luciferase Assay ◽  
Microrna Target ◽  
Cardiac Looping

MicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during early cardiac development. By using whole mount in situ hybridization in developing chick embryos, with microRNA-specific LNA probes, we carried out a detailed study of miR-23b, miR-130a, miR-106a, and miR-100 expression during early stages of embryogenesis (HH3 to HH17). We also correlated those findings with putative microRNA target genes by means of mirWalk and TargetScan analyses. Our results demonstrate a dynamic expression pattern in cardiac precursor cells from the primitive streak to the cardiac looping stages for miR-23b, miR-130a, and miR-106a. Additionally, miR-100 is later detectable during cardiac looping stages (HH15-17). Interestingly, the sinus venosus/inflow tract was shown to be the most representative cardiac area for the convergent expression of the four microRNAs. Through in silico analysis we revealed that distinct Hox family members are predicted to be targeted by the above microRNAs. We also identified expression of several Hox genes in the sinus venosus at stages HH11 and HH15. In addition, by means of gain-of-function experiments both in cardiomyoblasts and sinus venosus explants, we demonstrated the modulation of the different Hox clusters, Hoxa, Hoxb, Hoxc, and Hoxd genes, by these microRNAs. Furthermore, we correlated the negative modulation of several Hox genes, such as Hoxa3, Hoxa4, Hoxa5, Hoxc6, or Hoxd4. Finally, we demonstrated through a dual luciferase assay that Hoxa1 is targeted by miR-130a and Hoxa4 is targeted by both miR-23b and miR-106a, supporting a possible role of these microRNAs in Hox gene modulation during differentiation and compartmentalization of the posterior structures of the developing venous pole of the heart.

scholarly journals Effect of miR-27b-5p on apoptosis of human vascular endothelial cells induced by simulated microgravity

APOPTOSIS ◽  
2019 ◽  
Vol 25 (1-2) ◽  
pp. 73-91 ◽  
Author(s):  
Yi-Kai Pan ◽  
Cheng-Fei Li ◽  
Yuan Gao ◽  
Yong-Chun Wang ◽  
Xi-Qing Sun
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
Target Gene ◽  
Simulated Microgravity ◽  
Target Genes ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Luciferase Assay ◽  
Qrt Pcr ◽  
Differentially Expressed Mirnas

AbstractWeightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and KEGG enrichment analysis were performed. The effects of these miRNAs on HUVECs apoptosis were evaluated by flow cytometry, Western blot and Hoechst staining. Furthermore, we obtained the target gene of miR-27b-5p by luciferase assay, qRT-PCR and Western blot. Finally, we investigated the relationship between this target gene and miR-27b-5p in HUVECs apoptosis under normal gravity or simulated microgravity. We found 29 differentially expressed miRNAs in HUVECs under simulated microgravity. Of them, the expressions of 3 miRNAs were validated by qRT-PCR. We demonstrated that miR-27b-5p affected HUVECs apoptosis by inhibiting zinc fingers and homeoboxes 1 (ZHX1). Our results reported here demonstrate for the first time that simulated microgravity can alter the expression of some miRNAs in HUVECs and miR-27b-5p may protect HUVECs from apoptosis under simulated microgravity by targeting ZHX1.

MicroRNA expression profiles of the cuttlefish (Sepiella japonica) during embryonic development

2020 ◽  
Vol 71 (1) ◽  
pp. 37-47
Author(s):  
Liyun Wang ◽  
Shaogang Li ◽  
Lele Xu ◽  
Yongqin Li ◽  
Huaxu Chen ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Target Genes ◽  
Developmental Process ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Development Stages ◽  
Model Animal ◽  
Differentially Expressed Mirnas ◽  
Mirna Sequencing ◽  
Sepiella Japonica

Abstract The Japanese spineless cuttlefish (Sepiella japonica) is an important economic species and model animal. Many studies suggested that microRNAs (miRNAs) play an important regulatory role in the embryonic development of this species. However, comparative miRNA profiles during embryogenesis of cuttlefish have not been reported before. Therefore, in this study, miRNA profiles were obtained from embryos of S. japonica from eye primordium formation to larval growing stage by miRNA sequencing. A total of 1528 known miRNAs and 203 novel miRNAs were identified during different development stages. Among which, 62 differentially expressed miRNAs among different development stages were identified. GO analysis indicated that the potential target genes for these differentially expressed miRNAs were involved in many GO terms including intracellular membrane-bounded organelle, cell morphogenesis, regulation of developmental process, etc. In addition, miRNA-mRNA network analysis indicated that many of the target genes of these differentially expressed miRNAs were involved in integral component of the membrane. In conclusion, our work provided a global view of miRNA expression profiles during embryonic development of S. japonica.

Abstract 11940: Mineralocorticoid Receptor Dysregulation by MicroRNA-135a in Bradycardic Arrhythmogenic Remodeling

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Eric Duong ◽  
Jiening Xiao ◽  
Khai Le Quang ◽  
Patrice Naud ◽  
Yan- F Shi ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Mineralocorticoid Receptor ◽  
Target Genes ◽  
Ventricular Remodeling ◽  
Ventricular Tachyarrhythmia ◽  
Target Prediction ◽  
Torsades De Pointes ◽  
Left Ventricular ◽  
Luciferase Assay ◽  
Microrna Target

Introduction: Complete atrioventricular block (CAVB) causes arrhythmogenic remodeling and increases the risk of Torsades de Pointes (TdP) arrhythmias. MicroRNAs (miRs) are key regulators of gene expression that contribute to cardiac remodeling. Here, we assess microRNA changes after CAVB and their potential significance in arrhythmogenic cardiac remodeling. Methods: CAVB was induced in mice via His bundle ablation. Expression of miRs was evaluated by pan-microRNA microarray with qPCR confirmation on samples from controls and at 24 hrs and 4 wks post-CAVB. Arrhythmias were detected by continuous monitoring. MicroRNA target prediction algorithms were used to identify potential target genes. Biological confirmation of targets was by luciferase assay and overexpression (OE) studies in HEK and H9c2 cells respectively. Results: TdP occurred within 24 hrs in 6/17 CAVB mice, vs no controls. Ventricular tachyarrhythmia episodes were frequent at 4 wks CAVB (212±83 per 24 hrs) and were not seen in controls. CAVB was followed by increased left ventricular (LV) dimension (by 31%, ***p<.001), LV mass (by 33%, *p<.05) and LV fractional shortening (by 33%*) at 4 wks. Of >400 miRs assayed, only miR-135a was altered at 24 hrs (downregulated by 96%***, Fig. A), with 70% decrease at 4 wks. TargetScan predicted miR-135a regulation of the mineralocorticoid receptor (MCR), encoded by the NR3C2 gene. miR-135a OE suppressed NR3C2 3’UTR reporter activity 3.2-fold* (n=5, Fig. B). miR-135a OE did not affect NR3C2 mRNA (Fig. C) but significantly reduced NR3C2 protein expression (n=4, Fig. D). Coexpression with anti-miR-135a eliminated the NR3C2 downregulating effect of miR-135a OE. Conclusions: The mineralocorticoid receptor, encoded by the NR3C2 gene, is translationally regulated by miR-135a, a microRNA that is downregulated in the heart following CAVB in mice. These results implicate miR-135a/mineralocorticoid modulation in arrhythmogenic ventricular remodeling caused by CAVB.

scholarly journals Heart Enhancers: Development and Disease Control at a Distance

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuefei Yuan ◽  
Ian C. Scott ◽  
Michael D. Wilson
Keyword(s):  
Gene Expression ◽  
Developmental Biology ◽  
Target Genes ◽  
Cardiac Development ◽  
State Of The Art ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Functional Genomic ◽  
Genomic Technologies ◽  
Genome Wide

Bound by lineage-determining transcription factors and signaling effectors, enhancers play essential roles in controlling spatiotemporal gene expression profiles during development, homeostasis and disease. Recent synergistic advances in functional genomic technologies, combined with the developmental biology toolbox, have resulted in unprecedented genome-wide annotation of heart enhancers and their target genes. Starting with early studies of vertebrate heart enhancers and ending with state-of-the-art genome-wide enhancer discovery and testing, we will review how studying heart enhancers in metazoan species has helped inform our understanding of cardiac development and disease.

scholarly journals Hox genes in the coordination of embryonic development. Model of hourglass in the description of vertebrate ontogenesis

2021 ◽  
Vol 11 (12) ◽  
pp. 24-37
Author(s):  
Sergey Dolomatov ◽  
Vera Kazakova ◽  
Walery Zukow
Keyword(s):  
Embryonic Development ◽  
Tissue Regeneration ◽  
Target Genes ◽  
Hox Genes ◽  
Development Model ◽  
Tissue Morphogenesis ◽  
Hox Proteins ◽  
Temporal And Spatial

The paper analyzes the role of HOX genes in the processes of embryonic development of vertebrates. Based on the analysis, it is concluded that HOX genes are the most important regulators of embryonic development. The HOX genes predominantly realize their influence through specific HOX proteins that have the ability to regulate the expression of target genes. The order of expression of the HOX genes, as a rule, obeys the rule of temporal and spatial colinearity. This mechanism determines the temporal and spatial course of tissue morphogenesis during embryonic development and tissue regeneration in organisms that have reached the stage of maturity. The process of embryo morphogenesis, determined by highly conserved HOX genes, explains the appearance of the phylotypic period - the stage of embryonic development of vertebrates, at which embryos of different classes of vertebrates have distinct morphological similarities.

3 ANALYSIS OF HOX EXPRESSION IN BOVINE OOCYTES AND EARLY EMBRYOS

2010 ◽  
Vol 22 (1) ◽  
pp. 159
Author(s):  
D. Paul ◽  
W. Sonnet ◽  
R. Rezsohazy ◽  
I. Donnay
Keyword(s):  
Embryonic Development ◽  
Rna Polymerase Ii ◽  
Oocyte Maturation ◽  
Hox Genes ◽  
Early Stage ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Main Body ◽  
Bovine Oocytes

HOX genes encode transcription factors known to play a major role in patterning the main body axis of vertebrate embryos from the gastrulation stage onward. A few studies have provided evidence that some HOX genes might be expressed before implantation in mammalian embryos. Translation of maternally inherited transcripts is regulated by modifications of the poly(A) tail length until embryonic genome activation (EGA), occurring during the 4th cell cycle in the bovine. The objective of this work was to establish the expression pattern of various HOX genes and to study the polyadenylation of their transcripts during oocyte maturation and early embryonic development. Pools of 20 bovine oocytes before and after in vitro maturation and 20 in vitro-produced embryos at different stages of development up to the blastocyst stage were collected. Three to 12 pools were used for each stage. RNA was extracted and reverse transcribed (RT) using random hexamers. Quantitative real-time PCR (qPCR) was performed to establish expression profiles of 4 HOX genes: HOXD1, HOXA3, HOXB9, and HOXC9. Two distinct patterns of expression were observed. First, relative amounts of HOXD1, HOXA3, and HOXC9 were lower in morulae and blastocysts than in oocytes. On the other hand, relative expression of HOXB9 increased between the 5 to 8 cell stage and the morula stage (Mann-Whitney, P < 0.05). Those expression patterns were not modified when embryos were cultured in presence of α-amanitin, a RNA polymerase II inhibitor, indicating the maternal origin of the transcripts until EGA. Total amount of mRNAs, estimated by RT-qPCR with random hexamers, was stable for all studied genes during oocyte maturation. The relative amount of polyadenylated GAPDH mRNAs, estimated by RT-qPCR with poly(dT), decreased greatly in mature oocytes compared with immature oocytes indicating massive deadenylation of those transcripts. The relative amount of polyadenylated HOXC9 transcripts decreased slightly but significantly during oocyte maturation (Mann-Whitney, P < 0.05).The relative amount of polyadenylatedm RNAs corresponding to HOXD1, HOXA3, and HOXB9 was stable during oocyte maturation. This indicates that those transcripts escape the default deadenylation pathways followed by housekeeping genes. This experiment has been repeated 3 to 4 times. In conclusion, we confirmed the presence of HOXD1, HOXA3, HOXB9, and HOXC9 transcripts in bovine oocytes and early-stage embryos. Their role during oocyte maturation and the first stages of embryonic development will be investigated through loss of function studies. This work is funded by the Fonds National de la Recherche Scientifique (Belgium).

Cryptotanshinone Suppresses Liver Fibrosis by Attenuating Epithelial-Mesenchymal Transition through Targeting Hedgehog Pathway

2020 ◽  
Vol 20 ◽  
Author(s):  
Shurong Ren ◽  
Qizhen Yue ◽  
Qiubo Wang ◽  
Yanli Zhang ◽  
Bei Zhang
Keyword(s):  
Animal Model ◽  
Liver Fibrosis ◽  
Liver Diseases ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Chronic Liver ◽  
Luciferase Assay ◽  
Induced Expression ◽  
Mesenchymal Transition ◽  
Realtime Pcr

Background: Chronic liver damages from viral infection or alcohol abuse result in liver fibrosis, which is a key pathological event in many types of liver diseases. Discovering new anti-fibrosis agents may provide alternative solutions to manage chronic liver diseases. Methods: We first used CCl4 induced liver fibrosis animal model to evaluate the beneficial effects of Cryptotanshinone (CRY). We next explored target miRNAs regulated by CRY in hepatocytes using microarray. The target miRNA candidate was confirmed with realtime-PCR. We also elucidated the downstream target and pathway directly regulated by the miRNA using luciferase assay, western blotting and Epithelial–Mesenchymal Transition (EMT) markers quantification. Lastly, we confirmed CRY induced expression changes of the target genes in vivo. Results: CRY oral administration markedly alleviated the liver injury caused by CCl4. miRNAs expression profiling and realtime-PCR validation revealed miR-539-3p was directly induced by CRY around 4 folds. The induction of miR-539-3p suppressed SMO expression and antagonized Hedgehog (Hh) pathway. Independently CRY treatment suppressed SMO and inhibited EMT process in hepatocytes. The CRY induced expression changes of both miR-539-3p (~ 2 folds increase) and SMO (~ 60% decrease) in livers were validated in animal model. Conclusion: Our study supported CRY could inhibit liver fibrosis by targeting Hh pathway during EMT. CRY could be used as anti-fibrosis agent candidate for managing chronic liver damages.

scholarly journals Hox dosage contributes to flight appendage morphology in Drosophila

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachel Paul ◽  
Guillaume Giraud ◽  
Katrin Domsch ◽  
Marilyne Duffraisse ◽  
Frédéric Marmigère ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Differential Expression ◽  
Hox Genes ◽  
Expression Profiles ◽  
Fruit Fly ◽  
Insect Species ◽  
Wing Morphology ◽  
Hox Proteins ◽  
Spatial Expression ◽  
Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

scholarly journals Genome-wide transcriptome profiling uncovers differential miRNAs and lncRNAs in ovaries of Hu sheep at different developmental stages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samina Shabbir ◽  
Prerona Boruah ◽  
Lingli Xie ◽  
Muhammad Fakhar-e-Alam Kulyar ◽  
Mohsin Nawaz ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Differentially Expressed ◽  
Ovary Development ◽  
Estrogen Metabolism ◽  
Genome Wide ◽  
Micro Rnas ◽  
Hu Sheep

AbstractOvary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep.

scholarly journals The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chao Guo ◽  
Ya-yue Gao ◽  
Qian-qian Ju ◽  
Chun-xia Zhang ◽  
Ming Gong ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prediction Model ◽  
Hox Genes ◽  
Expression Profiles ◽  
Penalized Regression ◽  
Diagnostic Utility ◽  
Lasso Regression ◽  
Hub Genes ◽  
Npm1 Mutation ◽  
Genetic Abnormalities

Abstract Background The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA. Methods We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and ‘WGCNA’ package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R2 ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by ‘glmnet’ package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model. Results A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the ‘lightyellow’ module for NPM1 mutation, the ‘saddlebrown’ module for RUNX1 mutation, the ‘lightgreen’ module for TP53 mutation). ORA revealed that the ‘lightyellow’ module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The ‘saddlebrown’ module was enriched in immune response process. And the ‘lightgreen’ module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743–0.79). Conclusions We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. The 6-gene prediction model for AML survival was developed and validated by multiple datasets.

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