Identification of miRNAs-mediated seed and stone-hardening regulatory networks and their signal pathway of GA-induced seedless berries in grapevine (V. vinifera L.)

Abstract Background Stone-hardening stage is crucial to the development of grape seed and berry quality. A significant body of evidence supports the important roles of MicroRNAs in grape-berry development, but their specific molecular functions during grape stone-hardening stage remain unclear. Results Here, a total of 161 conserved and 85 species-specific miRNAs/miRNAs* (precursor) were identified in grape berries at stone-hardening stage using Solexa sequencing. Amongst them, 30 VvmiRNAs were stone-hardening stage-specific, whereas 52 exhibited differential expression profiles during berry development, potentially participating in the modulation of berry development as verified by their expression patterns. GO and KEGG pathway analysis showed that 13 VvmiRNAs might be involved in the regulation of embryo development, another 11 in lignin and cellulose biosynthesis, and also 28 in the modulation of hormone signaling, sugar, and proline metabolism. Furthermore, the target genes for 4 novel VvmiRNAs related to berry development were validated using RNA Ligase-Mediated (RLM)-RACE and Poly(A) Polymerase-Mediated (PPM)-RACE methods, and their cleavage mainly occurred at the 9th–11th sites from the 5′ ends of miRNAs at their binding regions. In view of the regulatory roles of GA in seed embryo development and stone-hardening in grape, we investigated the expression modes of VvmiRNAs and their target genes during GA-induced grape seedless-berry development, and we validated that GA induced the expression of VvmiR31-3p and VvmiR8-5p to negatively regulate the expression levels of CAFFEOYL COENZYME A-3-O-METHYLTRANSFERASE (VvCCoAOMT), and DDB1-CUL4 ASSOCIATED FACTOR1 (VvDCAF1). The series of changes might repress grape stone hardening and embryo development, which might be a potential key molecular mechanism in GA-induced grape seedless-berry development. Finally, a schematic model of miRNA-mediated grape seed and stone-hardening development was proposed. Conclusion This work identified 30 stone-hardening stage-specific VvmiRNAs and 52 significant differential expression ones, and preliminary interpreted the potential molecular mechanism of GA-induced grape parthenocarpy. GA negatively manipulate the expression of VvCCoAOMT and VvDCAF1 by up-regulation the expression of VvmiR31-3p and VvmiR8-5p, thereby repressing seed stone and embryo development to produce grape seedless berries.

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Study on miRNAs-Mediated Seed and Stone-Hardening Regulatory Networks and the Mechanism of miRNAs’ Manipulating Gibberellin-Induced Seedless Berries in Grapevine (Vitis vinifera L.)

10.21203/rs.3.rs-101517/v1 ◽

2020 ◽

Author(s):

Chen Wang ◽

Wenran Wang ◽

子文宿 ◽

Mostafa Abdelrahman ◽

Songtao Jiu ◽

...

Keyword(s):

Embryo Development ◽

Target Genes ◽

Expression Profiles ◽

Expression Patterns ◽

Lignin Biosynthesis ◽

Pcr Analysis ◽

Vitis Vinifera L ◽

Schematic Model ◽

Berry Development ◽

Seedless Grape

Abstract A significant body of evidence supports the important roles of miRNAs in grape berry developments. However, their specific molecular functions during stone-hardening stage development remain unclear. Here, a total of 161 conserved and 85 species-specific miRNAs/miRNAs*(precursor) were identified in grape stone hardening stage berries using Solexa sequencing. Out of them, 30 VvmiRNAs were tissue-specific and identified as stone-hardening related to VvmiRNAs, whereas 52 exhibited differential expression profiles during berry development, potentially participating in modulation of development, and qRT-PCR analysis verified their expression patterns. Interestingly, high SNP variations in VvmiRNA sequences might result into generation of new VvmiRNA family members like VvmiR168, VvmiR479, VvmiR3636 families and so on. Through GO and KEGG pathway analyses, we revealed that 13 VvmiRNAs involved in the regulation of embryo development, 11 in lignin and cellulose biosynthesis, and 28 in the modulation of hormone signaling, sugar and proline metabolism. Furthermore, the target genes for novel VvmiRNAs related to berry development were validated using RLM-RACE and PPM-RACE methods, and it was revealed their cleavage sites mainly happened at the 9th-11th sites from the 5’ ends of miRNAs at their binding regions. The potential roles of these VvmiRNAs in gibberellins repressing grape stone-hardening and embryo development by potentially inducing the expression of VvmiR31-3p and VvmiR8-5p to increase the cleavage product accumulation levels of corresponding target genes like lignin biosynthesis genes, CAFFEOYL COENZYME A-3-O-METHYLTRANSFERASE (VvCCoAOMT) and DDB1-CUL4 ASSOCIATED FACTOR1 (VvDCAF1), as a potential key molecular mechanism involved in GA-induced grape seedless berry development. Based on the characterization of stone-hardening stage related to VvmiRNAs, a schematic model of miRNA-mediated grape seed and stone-hardening development was proposed in this work. This is the first report about the regulatory role of VvmiRNAs in the regulation of stone-hardening stage of grape berries, which provides valuable genetic information for the breeding of seedless grape varieties.

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Expression profiling of ileal mucosa in asthma reveals upregulation of innate immunity and genes characteristic of Paneth and goblet cells

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00584-9 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Jan K. Nowak ◽

Marzena Dworacka ◽

Nazgul Gubaj ◽

Arystan Dossimov ◽

Zhumabek Dossimov ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Differential Expression ◽

Expression Profiles ◽

Differential Expression Analysis ◽

Goblet Cells ◽

Ileal Mucosa ◽

Significant Differential Expression ◽

Immune Genes ◽

Asthma Patients

Abstract Background The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Methods Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Results Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Conclusion Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.

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Thyrotroph embryonic factor (TEF) is differentially expressed in high-grade serous ovarian cancers.

10.31219/osf.io/djec5 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Transcription Factor ◽

Differential Expression ◽

Expression Profiles ◽

Gynecologic Cancer ◽

Bzip Transcription Factor ◽

High Grade ◽

Significant Differential Expression ◽

Primary Tumors ◽

Embryonic Factor

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We previously reported differential expression of the PAR-bZIP transcription factor HLF in HGSC (4). Here, we report significant differential expression of a second PAR-bZIP transcription factor, thyrotroph embryonic factor (TEF) (5) in high-grade serous ovarian tumors.

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Abstract WP120: MicroRNA Expression in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.wp120 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Janhavi M Modak ◽

Meaghan A Roy-O’Reilly ◽

Sarah E Conway ◽

Liang Zhu ◽

Louise D McCullough

Keyword(s):

Ischemic Stroke ◽

Differential Expression ◽

Expression Profiles ◽

Outpatient Setting ◽

Microrna Expression ◽

Neurological Deficits ◽

Stroke Patients ◽

Significant Differential Expression ◽

Blood Samples ◽

Mrna Targets

Background and Purpose: MicroRNAs (miRNAs) are a class of endogenous small non-coding ribonucleic acids that regulate gene expression and can impact cellular function by suppressing or activating downstream mRNA targets. Pre-clinical studies in animal models of stroke have demonstrated specific changes in miRNA expression profiles after ischemic stroke. Methods: Patients admitted to Hartford Hospital from January 2011 - March 2014 were considered for this study. Blood samples were collected within 24 hours of stroke presentation. miRNA profiles from peripheral blood samples of ischemic stroke patients were compared to controls. Patients with acute middle cerebral artery (MCA) cardioembolic strokes (based on TOAST criteria) were included (n=16). Blood collected from patients with no acute neurological deficits in an outpatient setting served as controls (n=8). Individuals with a history of active cancer, neoplastic brain lesions or traumatic brain injury were excluded. Based on literature review, 173 miRNAs were selected to assess for differential expression between cases and controls. miRNA profiling was conducted at Exiqon Services, Denmark, using miRCURY LNA™ microRNA Array. Statistical analysis was performed using SAS. Results: In patients with acute ischemic strokes, a statistically significant differential expression was observed in 14 miRNAs as compared to controls. MicroRNAs miR-1273e, miR-5187-3p were found to be downregulated in stroke patients (p=0.01). Other miRNAs showing a significant downregulation included let 7e-5p (p=0.03); miR-4709-3p, miR-4756-3p, miR-5584-3p, miR-647 (p=0.02); miR-4742-3p (p=0.03); miR-4764-5p, miR-4531 and miR-2116-5p (p=0.04). MicroRNAs miR-664a-3p (p=0.02), miR-943 (p=0.04) and miR-145-5p (p=0.03) were significantly upregulated. Differential expression in males and females was not observed. Conclusion: Ischemic stroke patients show a differential microRNA expression profile as compared to controls. Further studies can help identify microRNA signatures as well as the downstream targets involved in the ischemic stroke molecular cascade.

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Differential expression of RAS-like estrogen regulated growth inhibitor in human epithelial ovarian cancer.

10.31219/osf.io/m4zad ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Differential Expression ◽

Fallopian Tube ◽

Expression Profiles ◽

Growth Inhibitor ◽

High Grade ◽

Significant Differential Expression ◽

Primary Tumors ◽

Ovarian Cancers

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding RAS-like estrogen regulated growth inhibitor, RERG, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. RERG expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. In a separate dataset, we discovered significant differential expression of a non-coding RNA transcribed from the RERG locus, RERG-AS1, in the tumors of patients with epithelial ovarian cancer when comparing tumors based on disease progression. RERG expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of RERG is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. RERG may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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Restored lncRNAs After ART Therapy Have Potential Key Roles in the Recovery From AIDS

10.21203/rs.3.rs-871811/v1 ◽

2021 ◽

Author(s):

Yingying Zhou ◽

Yuqing Huang ◽

Tielong Chen ◽

Wenjia Hu ◽

Xiaoping Chen ◽

...

Keyword(s):

Hiv Infection ◽

Differential Expression ◽

Art Therapy ◽

Target Genes ◽

Mononuclear Cells ◽

Expression Profiles ◽

Effective Control ◽

Rna Seq ◽

Peripheral Blood Mononuclear ◽

Hiv Pathogenesis

Abstract Background: Many studies have shown that long noncoding RNAs (lncRNAs) derived from the host and human immunodeficiency virus (HIV) itself play important roles in virus-host interactions and viral pathogenesis. To identify potential key lncRNAs in the regulation of HIV pathogenesis, transcriptome analysis of peripheral blood mononuclear cells (PBMCs), which were derived from 6 HIV/acquired immunodeficiency syndrome (AIDS) subjects pre-HAART and post-HAART with effective control of plasma viremia (<20 HIV RNA copies/ml) and 6 healthy subjects, was performed by RNA sequencing (RNA-seq).Results: We identified a total of 974 lncRNAs whose expression levels were restored to normal after ART therapy. The results of the cis-acting analysis showed that only six lncRNAs have cis-regulated target genes, among which the target gene RP11-290F5.1, interferon regulatory factors 2 (IRF2), could promote HIV replication. We also identified lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression between pre- and post-HAART, and the differences were significant. We selected lncRNA CTB-119C2.1 for qRT–PCR verification, and the results were consistent with those of RNA-seq. RAB3A and GADD45A, two of the lncRNA CTB-119C2.1-associated genes, have been shown to be associated with HIV infection. KEGG analysis of lncRNA CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway or pathways related to cell circulation and DNA replicationConclusion: In this study, we used RNA-seq to systematically compare the expression profiles of lncRNAs in HIV subjects between untreated and treated time points. We successfully identified some lncRNAs with differential expression during certain periods (no HIV infection, HIV infection before treatment, and after treatment). Their expression is associated with viral loads, and some of their regulating genes were found to be involved in HIV pathogenesis through bioinformatic analysis. These findings could help to reveal the underlying molecular mechanism of the progression of AIDS.

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Potential function and molecular mechanism of circRNAs involved in idiopathic pulmonary fibrosis

10.21203/rs.3.rs-15519/v1 ◽

2020 ◽

Author(s):

Fangwei Li ◽

Hong Wang ◽

Hongyan Tao ◽

Fanqi Wu ◽

Dan Wang ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Molecular Mechanism ◽

Target Genes ◽

Expression Profiles ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Circular Rnas

Abstract Background: Recent studies have found a regulatory role of circular RNAs (circRNAs) in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the function and underlying molecular mechanism of circRNAs involved in IPF are uncertain and incomplete. This study aimed to further provide some critical information for the circRNA function in IPF using bioinformatic analysis. Methods: We searched in the NCBI (National Center for Biotechnology Information) Gene Expression Omnibus (GEO) database to find the circRNA expression profiles of human IPF. The microarray data GSE102660 was obtained and differentially expressed circRNAs were identified through R software. Results: 6 significantly up-regulated and 13 significantly down-regulated circRNAs were identified involved in the pathogenesis of IPF. The binding sites of miRNAs for each differentially expressed circRNA were also predicted and circRNA-miRNA-mRNA networks were constructed for the most up-regulated hsa_circ_0004099 and down-regulated hsa_circ_0029633. In addition, GO and KEGG enrichment analysis revealed the molecular function and enriched pathways of the target genes of circRNAs in IPF.Conclusion: These findings suggest that candidate circRNAs might serve an important role in the pathogenesis of IPF. Therefore, these circRNAs might be potential biomarkers for diagnosis and promising targets for treatment of IPF, which still need further veriﬁcation in vivo and in vitro.

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Characterization of the microRNA Expression Profiles in the Goat Kid Liver

Frontiers in Genetics ◽

10.3389/fgene.2021.794157 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xiaodong Zhao ◽

Zhibin Ji ◽

Rong Xuan ◽

Aili Wang ◽

Qing Li ◽

...

Keyword(s):

Differential Expression ◽

Fatty Acid Synthase ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Expression Patterns ◽

Metabolic Process ◽

Liver Development ◽

Hormone Synthesis ◽

Liver Tissues

The liver is the largest digestive gland in goats with an important role in early metabolic function development. MicroRNAs (miRNA) are crucial for regulating the development and metabolism in the goat liver. In the study, we sequenced the miRNAs in the liver tissues of the goat kid to further research their regulation roles in early liver development. The liver tissues were procured at 5-time points from the Laiwu black goats of 1 day (D1), 2 weeks (W2), 4 weeks (W4), 8 weeks (W8), and 12 weeks (W12) after birth, respectively with five goats per time point, for a total of 25 goats. Our study identified 214 differential expression miRNAs, and the expression patterns of 15 randomly selected miRNAs were examined among all five age groups. The Gene ontology annotation results showed that differential expression miRNA (DE miRNA) target genes were significantly enriched in the fatty acid synthase activity, toxin metabolic process, cell surface, and antibiotic metabolic process. The KEGG analysis result was significantly enriched in steroid hormone synthesis and retinol metabolism pathways. Further miRNA-mRNA regulation network analysis reveals 9 differently expressed miRNA with important regulation roles. Overall, the DE miRNAs were mainly involved in liver development, lipid metabolism, toxin related metabolism-related biological process, and pathways. Our results provide new information about the molecular mechanisms and pathways in the goat kid liver development.

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Deep Sequencing of Guinea Pig (Cavia Porcellus) Lung Small RNAs Reveals Differential Expression of microRNAs between Non-infected and BCG-Infected Lungs

10.21203/rs.3.rs-771411/v1 ◽

2021 ◽

Author(s):

Xiaoqi jing ◽

Biqiong Jiang ◽

Long Cheng ◽

Yong Li

Keyword(s):

Immune Responses ◽

Guinea Pig ◽

Differential Expression ◽

Deep Sequencing ◽

Target Genes ◽

Transforming Growth Factor ◽

Expression Profiles ◽

Mitogen Activated Protein Kinase ◽

Public Health Burden ◽

Small Noncoding Rnas

Abstract Background: Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection remains a major public health burden worldwide. It has been well documented that a group of small noncoding RNAs, microRNAs (miRNAs) are involved in the development and pathogenesis many diseases, including the TB. Guinea pigs are considered as one of the best animal models for biomedical research in TB, the potential roles of miRNAs in the innate immune regulation of guinea pig lung against Mtb infection are not well understood. Methods: In this study, we investigated the differential expression of miRNA profiles between the un-infected lungs and Mycobacterium bovis bacillus Calmette-Guérin (BCG)-infected lungs of guinea pigs via deep sequencing and bioinformatics analysis. Results: A total of 2508 miRNAs were identified, among them 1187 were conserved miRNAs and 56 were novel miRNAs in the uninfected lungs, and 1202 were identified as conserved miRNAs and 63 were novel miRNAs in the BCG-infected lungs. Interestingly, comparison analysis further identified 902 co-expressed miRNAs and 585 distinct miRNAs between these two groups. Of the 15 most abundantly conserved miRNAs in guinea pig lungs, which belong to 7 miRNA families, including miR23, miR29, miR145, miR320, miR378, miR451, and miR423. 13 of these 15 most abundant miRNAs were significantly downregulated and 2 of them were significantly upregulated in the BCG-infected lungs. Individually, miRNA Let-7f-5p, let-7f, let-7-5p and let-7b-5p were the most abundant in both profiles of the non-infected and BCG-infected guinea pig lungs. The predicted target genes of specific miRNAs found in guinea pig lungs were involved in regulation signaling pathways related to immune responses, including Toll-like receptors (TLRs), nuclear factor (NF)-kappa B, Wnt, mitogen-activated protein kinase (MAPK), and transforming growth factor (TGF)-beta signaling, as well as related to autophagy signaling mTOR and apoptotic molecule p53. Conclusions: These data of comprehensive analysis of miRNA transcriptome demonstrated the differential expression profiles of miRNAs during M. tuberculosis infection of guinea pig lungs. These results could facilitate the future exploitation of the roles of miRNAs in regulation of immune responses to M. tuberculosis infection using the guinea pig model.

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Comparative profiling of exosomal miRNAs in human adult peripheral and umbilical cord blood plasma by deep sequencing

Epigenomics ◽

10.2217/epi-2019-0213 ◽

2020 ◽

Vol 12 (10) ◽

pp. 825-842 ◽

Cited By ~ 1

Author(s):

Sirui Huang ◽

Zhenlin Tang ◽

Yuheng Wang ◽

Danliang Chen ◽

Jinhua Li ◽

...

Keyword(s):

Cord Blood ◽

Differential Expression ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Target Genes ◽

Human Peripheral Blood ◽

Expression Profiles ◽

Small Rna Sequencing ◽

Exosomal Mirnas ◽

Differentially Expressed Mirnas

Aim: To assess differential expression profiles of miRNAs in exosomes derived from human peripheral blood (PB) and umbilical cord blood (UCB). Materials & methods: Small RNA sequencing was performed to characterize the miRNA expression in plasma exosomes processed from UCB of five healthy newborns and PB of five normal adult volunteers, and differentially expressed miRNAs were further analyzed. Results: A total of 65 exosomal miRNAs, including 46 upregulated and 19 downregulated, showed differential expression between UCB and PB. Target genes of these miRNAs were mainly enriched in signaling pathways associated with pregnancy, cancers, cell mobility and nervous system. Conclusion: Exosomal miRNAs may have essential roles in the biological functions of UCB, suggesting the therapeutic and biomarker potentials of exosomes in UCB.

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