Differential expression of lncRNA in the hypothalamus-pituitary-gonadal axis of Wanxi white geese during laying and broodiness periods.

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This study explored the molecular mechanism of the hypothalamus-pituitary-gonadal (HPG) axis on the regulation of brooding behavior and laying performance of Wanxi white geese (WWG). The transcriptome of the hypothalamus, pituitary, and ovarian tissues of laying and brooding WWG was sequenced to identify genes and lncRNAs that may be important in regulating the egg-laying performance and broodiness behavior of WWG. This study sequenced the lncRNA on the hypothalamus, pituitary, and ovarian tissues of WWG white geese during laying and broodiness periods to determine the differentially expressed lncRNA (DElncRNA) in the hypothalamus-pituitary-ovary (HPO) axis. lncRNA-miRNA-mRNA (ceRNA) regulatory network was constructed using selected DEGs, DEMs, and DElncRNAs. Differentially expressed DEGs, DEMs, and DElncRNAs were further confirmed via real-time quantitative polymerase chain reaction. The dual luciferase reporter gene assay confirmed a targeting relationship between the MST RG.1166. 1/miR-450-x/SOX8 axis. A total of 184 ( BH vs LH ), 180 ( BP vs LP ), and 880 ( BO vs LO ) differentially expressed lncRNAs were screened. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis showed that the DElncRNAs significantly enriched Steroid hormone biosynthesis, Neuroactive ligand-receptor interaction, Calcium signaling, and other pathways. The lncRNA-miRNA-mRNA (ceRNA) regulatory network of laying performance and nesting behavior was constructed through the database. MSTRG.1166.1-miR-450-x-SOX8, MSTRG. 7163.5-miR-182-x-CSMD1, XR_007167835.1- miR-277-z-RAB3B, MSTRG. 7163.5-miR-151-y-PAQR9, MSTRG.4615.2-miR-96-x-DAPK1, XR_007164924.1-miR-144-y-TFPI, XR_007161186.1-miR-205-x-THRB, MSTRG.10196.1/ XR_001206277.2-miR-339-x-TRAF4, and MSTRG.9442.1-miR-9-y-FBN3 may play an important role in the ovarian development of WWG. The dual luciferase reporter gene assay confirmed a targeting relationship between the MSTRG.1166.1/miR-450-x/SOX8 axis. The results of this study systematically expounded on how the HPG axis involves lncRNA, miRNA, and mRNA to post-transcriptionally regulate the broodiness behavior and laying performance of WWG. The results will improve knowledge of the complex interaction between lncRNA and genes controlling laying performance and broodiness behavior.

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  • Cite Count Icon 4
  • 10.1186/s12920-021-00894-2
Integrated analysis of differentially expressed genes and construction of a competing endogenous RNA network in human Huntington neural progenitor cells
  • Feb 12, 2021
  • BMC medical genomics
  • Xiaoping Tan + 3 more

BackgroundHuntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking.MethodsIn this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein–protein interaction (PPI) network for mRNAs interacting with these lncRNAs.ResultsWe identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors.ConclusionsOur research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.

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  • Cite Count Icon 12
  • 10.3390/biom13020390
Preliminary Transcriptome Analysis of Long Noncoding RNA in Hypothalamic-Pituitary-Mammary Gland Axis of Dairy Cows under Heat Stress.
  • Feb 18, 2023
  • Biomolecules
  • Hanfang Zeng + 4 more

Heat stress (HS) is directly correlated to mammary gland dysfunction in dairy cows, especially in summer. The hypothalamic-pituitary-mammary gland axis (HPM axis) plays an important role in the regulation of stress response and lactation physiology in heat-stressed dairy cows. The aim of this study was to explore the lncRNA profile, and the competitive endogenous RNA (ceRNA) regulatory network in hypothalamus, pituitary, and mammary gland tissues of heat-stressed and normal dairy cows. We performed RNA sequencing (RNA-seq) to identify differentially expressed (DE) lncRNAs, and the ceRNA regulatory network was established in HPM-axis-related tissues. Our results showed that a total of 13, 702 and 202 DE lncRNAs were identified in hypothalamus, pituitary, and mammary glands, respectively. Of lncRNAs, 8, 209 and 45 were up-regulated, and 5, 493 and 157 lncRNAs were down-regulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DE lncRNAs target genes that might play a role in hormone synthesis, secretion and action, apoptosis, mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR) signaling pathway. Moreover, the ceRNA regulatory network associated with the MAPK signaling pathway in HPM-axis-related tissues contains 3286 lncRNA-mRNA pairs. Furthermore, the ceRNA regulatory network associated with apoptosis, prolactin, AMPK, and mTOR signaling pathway in the mammary gland contains 772 lncRNA-mRNA pairs. Thus, some lncRNAs may be involved in the regulation of stress response and the physiological process of lactation. The changes in lncRNA expression profiles and ceRNAs (lncRNA-miRNA-mRNA) in HPM-axis-related tissues are the key to affect the stress response and lactation physiology of dairy cows under HS, which provide a theoretical basis for the molecular mechanism in the stress response of HPM-axis-related tissues in dairy cows under HS.

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  • Cite Count Icon 60
  • 10.1155/2020/8162524
High-Throughput Sequencing and Exploration of the lncRNA-circRNA-miRNA-mRNA Network in Type 2 Diabetes Mellitus.
  • Jan 1, 2020
  • BioMed Research International
  • Fang Yang + 10 more

Objective Long noncoding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in diabetes research. However, there are still many unknown lncRNAs and circRNAs that need further study. The aim of this study is to identify new lncRNAs and circRNAs and their potential biological functions in type 2 diabetes mellitus (T2DM). Methods RNA sequencing and differential expression analysis were used to identify the noncoding RNAs (ncRNAs) and mRNAs that were expressed abnormally between the T2DM and control groups. The competitive endogenous RNA (ceRNA) regulatory network revealed the mechanism of lncRNA and circRNA coregulating gene expression. The biological functions of lncRNA and circRNA were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The candidate hub mRNAs were selected by the protein-protein interaction (PPI) network and validated by using the Gene Expression Omnibus (GEO) database. Results Differential expression analysis results showed that 441 lncRNAs (366 upregulated and 75 downregulated), 683 circRNAs (354 upregulated and 329 downregulated), 93 miRNAs (63 upregulated and 30 downregulated), and 2923 mRNAs (1156 upregulated and 1779 downregulated) were identified as remarkably differentially expressed in the T2DM group. The ceRNA regulatory network showed that a single lncRNA and circRNA can be associated with multiple miRNAs, and then, they coregulate more mRNAs. Functional analysis showed that differentially expressed lncRNA (DElncRNA) and differentially expressed circRNA (DEcircRNA) may play important roles in the mTOR signaling pathway, lysosomal pathway, apoptosis pathway, and tuberculosis pathway. In addition, PIK3R5, AKT2, and CLTA were hub mRNAs screened out that were enriched in an important pathway by establishing the PPI network. Conclusions This study is the first study to explore the molecular mechanisms of lncRNA and circRNA in T2DM through the ceRNA network cofounded by lncRNA and circRNA. Our study provides a novel insight into the T2DM from the ceRNA regulatory network.

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  • Cite Count Icon 24
  • 10.1111/jcmm.15424
Identification of circRNA and mRNA expression profiles and functional networks of vascular tissue in lipopolysaccharide-induced sepsis.
  • May 25, 2020
  • Journal of Cellular and Molecular Medicine
  • Mu‐Wen Nie + 3 more

Sepsis is the most common cause of death in intensive care units. This study investigated the circular RNA (circRNA) and mRNA expression profiles and functional networks of the aortic tissue in sepsis. We established a lipopolysaccharide (LPS)‐induced rat sepsis model. High‐throughput sequencing was performed on the aorta tissue to identify differentially expressed (DE) circRNAs and mRNAs, which were validated by real‐time quantitative polymerase chain reaction (RT‐qPCR). Bioinformatic analysis was carried out and coding and non‐coding co‐expression (CNC) and competing endogenous RNA (ceRNA) regulatory networks were constructed to investigate the mechanisms. In total, 373 up‐regulated and 428 down‐regulated circRNAs and 2063 up‐regulated and 2903 down‐regulated mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of mRNAs showed that the down‐regulated genes were mainly enriched in the process of energy generation. CNC and ceRNA regulatory networks were constructed with seven DE circRNAs. The results of functional enrichment analysis of CNC target genes revealed the important role of circRNAs in inflammatory response. The ceRNA network also highlighted the significant enrichment in calcium signalling pathway. Significant alterations in circRNAs and mRNAs were observed in the aortic tissue of septic rats. In addition, CNC and ceRNA networks were established.

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  • 10.3390/ijms26115161
Validation of Targeted Relationships of Novel circRNA803/lncRNA MSTRG.19726-oar-let-7a-CPEB1 ceRNA Networks, Key to Follicle Development in Single-Litter and Multi-Litter Sheep Based on Whole-Transcriptome Sequencing.
  • May 28, 2025
  • International journal of molecular sciences
  • Bo Gu + 4 more

The objective of this study is to investigate the molecular regulatory mechanisms of non-coding RNA (ncRNA) during the developmental process of multi-litter sheep ovaries and identify key regulatory genes that enhance the reproductive capacity of sheep. This study selected Small-Tail Han sheep (multi-litter sheep) and Ujumuqin sheep (single-litter sheep) as comparative models, constructed the expression profiles of ncRNAs and mRNAs in ovarian tissues, identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs, and performed target gene prediction along with functional and signaling pathway enrichment analyses. Reproduction-related pathways were further screened to construct competing endogenous RNA (ceRNA) regulatory networks (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA). Finally, the dual-luciferase reporter gene assay system was employed to perform the functional validation of the relevant targeted regulatory effects. A comprehensive screening identified 411 DE lncRNAs, 322 DE circRNAs, 26 DE miRNAs, and 29 DEGs from the ovarian tissues of Ujumqin and Small-Tail Han sheep. The results of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that the DE target genes were significantly enriched in pathways associated with cell dedifferentiation, the positive regulation of embryonic development, glycosaminoglycan biosynthesis, Hippo signaling, and other signaling pathways. To identify genes associated with reproductive processes, we performed differential expression screening followed by pathway enrichment analysis, which revealed significant enrichment in reproductive regulatory pathways. Based on these findings, we constructed a ceRNA regulatory network incorporating 22 DEGs, 17 DE lncRNAs, three DE circRNAs, and one DE miRNA. Our analysis revealed that oar-let-7a is involved in signaling pathways such as oocyte meiosis and Hippo, suggesting it may serve as a key miRNA regulating the trait of multiple offspring. The dual-luciferase reporter assay was employed to confirm that oar-let-7a directly targets and regulates the expression of CPEB1. Additionally, it was demonstrated that circRNA803 and lncRNA MSTRG.19726 function as molecular sponges to competitively bind and regulate oar-let-7a. These findings suggest that oar-let-7a mediates the expression of CPEB1 via circRNA803 and lncRNA MSTRG.19726 sponge adsorption, thereby regulating the process of follicular dominance in sheep. The qRT-PCR method was employed to validate the expression patterns of nine randomly selected DEGs, and the results corroborated the reliability of the RNA-seq sequencing data. This study investigated the coordinated regulatory mechanism of DE ncRNAs and their corresponding target genes, identifying a ceRNA network, circRNA803/lncRNA MSTRG.19726-oar-let-7a-CPEB1, which plays a critical role in regulating the process of follicular dominance in sheep. These findings provide fundamental data for uncovering the reproductive potential of sheep and facilitate a comprehensive understanding of their reproductive characteristics, which hold significant guiding implications for enhancing reproductive efficiency.

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  • 10.1016/j.psj.2024.104510
Comprehensive analysis of mRNA and miRNA differential expression profiles in the hypothalamus-pituitary-gonadal axis in laying and broodiness period of Wanxi white geese
  • Nov 9, 2024
  • Poultry Science
  • Xinwei Tong + 7 more

Comprehensive analysis of mRNA and miRNA differential expression profiles in the hypothalamus-pituitary-gonadal axis in laying and broodiness period of Wanxi white geese

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  • Cite Count Icon 10
  • 10.1186/s12938-021-00952-x
Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis
  • Nov 24, 2021
  • BioMedical Engineering OnLine
  • Yumiao Li + 10 more

BackgroundLung adenocarcinoma (LUAD) is the most common subtype of nonsmall-cell lung cancer (NSCLC) and has a high incidence rate and mortality. The survival of LUAD patients has increased with the development of targeted therapeutics, but the prognosis of these patients is still poor. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of LUAD. The purpose of this study was to identify novel abnormally regulated lncRNA–microRNA (miRNA)–messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks that may suggest new therapeutic targets for LUAD or relate to LUAD prognosis.MethodsWe used the SBC human ceRNA array V1.0 to screen for differentially expressed (DE) lncRNAs and mRNAs in four paired LUAD samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the DE lncRNAs and mRNAs. R bioinformatics packages, The Cancer Genome Atlas (TCGA) LUAD database, and Kaplan–Meier (KM) survival analysis tools were used to validate the microarray data and construct the lncRNA–miRNA–mRNA ceRNA regulatory network. Then, quantitative real-time PCR (qRT-PCR) was used to validate the DE lncRNAs in 7 LUAD cell lines.ResultsA total of 2819 DE lncRNAs and 2396 DE mRNAs (P < 0.05 and fold change ≥ 2 or ≤ 0.5) were identified in four paired LUAD tissue samples. In total, 255 of the DE lncRNAs were also identified in TCGA. The GO and KEGG analysis results suggested that the DE genes were most enriched in angiogenesis and cell proliferation, and were closely related to human cancers. Moreover, the differential expression of ENST00000609697, ENST00000602992, and NR_024321 was consistent with the microarray data, as determined by qRT-PCR validation in 7 LUAD cell lines; however, only ENST00000609697 was associated with the overall survival of LUAD patients (log-rank P = 0.029). Finally, through analysis of ENST00000609697 target genes, we identified the ENST00000609697–hsa-miR-6791-5p–RASL12 ceRNA network, which may play a tumor-suppressive role in LUAD.ConclusionENST00000609697 was abnormally expressed in LUAD. Furthermore, downregulation of ENST00000609697 and its target gene RASL12 was associated with poor prognosis in LUAD. The ENST00000609697–hsa-miR-6791-5p–RASL12 axis may play a tumor-suppressive role. These results suggest new potential prognostic and therapeutic biomarkers for LUAD.

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  • Cite Count Icon 1
  • 10.3389/fnagi.2024.1388655
Integrative analysis of plasma and substantia nigra in Parkinson's disease: unraveling biomarkers and insights from the lncRNA-miRNA-mRNA ceRNA network.
  • May 9, 2024
  • Frontiers in Aging Neuroscience
  • Ka-Yoon Chun + 1 more

Parkinson's disease (PD) is a rapidly growing neurological disorder characterized by diverse movement symptoms. However, the underlying causes have not been clearly identified, and accurate diagnosis is challenging. This study aimed to identify potential biomarkers suitable for PD diagnosis and present an integrative perspective on the disease. We screened the GSE7621, GSE8397-GPL96, GSE8397-GPL97, GSE20163, and GSE20164 datasets in the NCBI GEO database to identify differentially expressed (DE) mRNAs in the substantia nigra (SN). We also screened the GSE160299 dataset from the NCBI GEO database to identify DE lncRNAs and miRNAs in plasma. We then constructed 2 lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory networks based on the ceRNA hypothesis. To understand the biological function, we performed Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses for each ceRNA network. The receiver operating characteristic analyses (ROC) was used to assess ceRNA results. We identified 7 upregulated and 29 downregulated mRNAs as common DE mRNAs in the 5 SN datasets. In the blood dataset, we identified 31 DE miRNAs (9 upregulated and 22 downregulated) and 332 DE lncRNAs (69 upregulated and 263 downregulated). Based on the determined interactions, 5 genes (P2RX7, HSPA1, SLCO4A1, RAD52, and SIRT4) appeared to be upregulated as a result of 10 lncRNAs sponging 4 miRNAs (miR-411, miR-1193, miR-301b, and miR-514a-2/3). Competing with 9 genes (ANK1, CBLN1, RGS4, SLC6A3, SYNGR3, VSNL1, DDC, KCNJ6, and SV2C) for miR-671, a total of 26 lncRNAs seemed to function as ceRNAs, influencing genes to be downregulated. In this study, we successfully constructed 2 novel ceRNA regulatory networks in patients with PD, including 36 lncRNAs, 5 miRNAs, and 14 mRNAs. Our results suggest that these plasma lncRNAs are involved in the pathogenesis of PD by sponging miRNAs and regulating gene expression in the SN of the brain. We propose that the upregulated and downregulated lncRNA-mediated ceRNA networks represent mechanisms of neuroinflammation and dopamine neurotransmission, respectively. Our ceRNA network, which was associated with PD, suggests the potential use of DE miRNAs and lncRNAs as body fluid diagnostic biomarkers. These findings provide an integrated view of the mechanisms underlying gene regulation and interactions in PD.

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Comprehensive evaluation of differential long non-coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra.
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  • Experimental and Therapeutic Medicine
  • Jinghong Yuan + 8 more

Long non-coding RNAs (lncRNAs) are emerging as key regulators in gene expression; however, little is currently known regarding their role in cartilaginous endplate (CE) degeneration (CED) of cervical vertebra. The present study aimed to investigate the expression levels of lncRNAs and analyze their potential functions in CED of cervical vertebra in patients with cervical fracture and cervical spondylosis. Human competitive endogenous RNA (ceRNA) array was used to analyze lncRNA and mRNA expression levels in CE samples from patients with cervical fracture and cervical spondylosis, who received anterior cervical discectomy and fusion. Differentially expressed lncRNAs (DELs) or differentially expressed genes (DEGs) were identified and functionally analyzed, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. An lncRNA-microRNA(miRNA)-mRNA ceRNA regulatory network was constructed based on the DELs and DEGs, and the ceRNA network was visualized using Cytoscape 3.7.2 software. In total, one downregulated mRNA, one upregulated miRNA and five downstream regulated lncRNAs were identified using reverse transcription-quantitative PCR in CED and healthy CE samples. A total of 369 lncRNAs and 246 mRNAs were identified as differentially expressed in CE. The GO and KEGG analyses demonstrated that the majority of GO and KEGG enrichments were associated with CED. Furthermore, a ceRNA network was established, including 168 putative miRNA response elements, 189 upregulated and 37 downregulated lncRNAs and 47 upregulated and 10dow regulated DEGs. The present study analyzed the function of DEGs in the ceRNA network and filtered out the same items as in DEG-function enrichment analysis. These results provide a new perspective for an improved understanding of ceRNA-mediated gene regulation in cervical spondylosis, and provide a novel theoretical basis for further studies on the function of lncRNA in cervical spondylosis. However, further experiments are required to validate the results of the present study.

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  • 10.21037/tcr-22-842
Whole-genome identification and construction of the lncRNA-mRNA co-expression network in patients with actinic keratosis.
  • Nov 1, 2022
  • Translational Cancer Research
  • Chao Luan + 8 more

Actinic keratosis (AK) is a common premalignant lesion induced by chronic exposure to ultraviolet radiation and may develop into invasive cutaneous squamous carcinoma (cSCC). The identification of specific biomarkers in AK are still unclear. Long non-coding RNAs (lncRNAs), as transcripts of more than 200 nucleotides, significantly involving in multiple biologic processes, especially in the development of tumors. In our study, we obtained data from RNA-sequencing analysis using two AK lesion tissues and three normal cutaneous tissues to comparatively analyze the differentially expressed (DE) lncRNAs and messenger RNAs (mRNAs). Firstly, we used microarray analyses to identify DE lncRNAs and DE mRNAs. Secondly, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to analyze the primary function and find out significant pathways of these DE mRNA and lncRNAs. Finally, we used the top ten DE lncRNAs to construct a lncRNA-mRNA co-expression network. Our results showed that there were a total of 2,097 DE lncRNAs and 2,043 DE mRNAs identified. GO and KEGG analysis and the lncRNA-mRNA co-expression network (using the top 10 DE lncRNAs comprises 130 specific co-expressed mRNAs to construct) indicated that lncRNA uc011fnr.2 may negatively regulate SCIMP and Toll-like receptor 4 (TLR4) and play an important role in Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway of AK. lncRNA uc011fnr.2 may play an important role in JAK-STAT3 signaling pathway of AK by modulating SCIMP, TLR4 and IL-6. Further research is required to validate the value of lncRNA uc011fnr.2 in the progression of AK.

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  • 10.3892/ol.2016.5024
Bioinformatics analysis of the molecular mechanism of diffuse intrinsic pontine glioma
  • Aug 16, 2016
  • Oncology Letters
  • Lei Deng + 5 more

The present study aimed to elucidate key molecular mechanisms in the progression of diffuse intrinsic pontine glioma (DIPG). The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in the pediatric DIPG samples were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways of DEGs were enriched and analyzed. The protein-protein interaction (PPI) network of the DEGs was constructed and functional modules of the PPI network were disclosed using ClusterONE. A total of 679 DEGs (454 up- and 225 downregulated) were identified in the pediatric DIPG samples. DEGs were significantly enriched in various GO terms, and KEGG and Reactome pathways. The PPI network of upregulated (153 nodes and 298 connections) and downregulated (71 nodes and 124 connections) DEGs, and two crucial modules, were obtained. Downregulated genes in module 2, such as cholecystokinin (CCK), gastrin (GAST), adenylate cyclase 2 (brain) (ADCY2) and 5-hydroxytryptamine (serotonin) receptor 7 (HTR7), were significantly enriched in the calcium signaling pathway, the neuroactive ligand-receptor interaction pathway and in GO terms, such as the G-protein coupled receptor (GPCR) signaling pathway, while upregulated genes in module 1 were not enriched in any pathways or GO terms. CCK and GAST associated with the GPCR signaling pathway, HTR7 enriched in the neuroactive ligand-receptor interaction, and ADCY2 and HTR7 involved in the calcium signaling pathway may be key mechanisms playing crucial roles in the development and progression of DIPG.

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  • Cite Count Icon 11
  • 10.3389/fcell.2023.1185823
Integrated analysis of circRNA, lncRNA, miRNA and mRNA to reveal the ceRNA regulatory network of postnatal skeletal muscle development in Ningxiang pig
  • Jul 3, 2023
  • Frontiers in Cell and Developmental Biology
  • Zonggang Yu + 11 more

Introduction: The development of skeletal muscle is regulated by regulatory factors of genes and non-coding RNAs (ncRNAs).Methods: The objective of this study was to understand the transformation of muscle fiber type in the longissimus dorsi muscle of male Ningxiang pigs at four different growth stages (30, 90, 150, and 210 days after birth, n = 3) by histological analysis and whole transcriptome sequencing. Additionally, the study investigated the expression patterns of various RNAs involved in muscle fiber transformation and constructed a regulatory network for competing endogenous RNA (ceRNA) that includes circular RNA (circRNA)/long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA).Results: Histomorphology analysis showed that the diameter of muscle fiber reached its maximum at 150 days after birth. The slow muscle fiber transformation showed a pattern of initial decrease followed by an increase. 29,963 circRNAs, 2,683 lncRNAs, 986 miRNAs and 22,411 mRNAs with expression level ≥0 were identified by whole transcriptome sequencing. Furthermore, 642 differentially expressed circRNAs (DEc), 505 differentially expressed lncRNAs (DEl), 316 differentially expressed miRNAs (DEmi) and 6,090 differentially expressed mRNAs (DEm) were identified by differential expression analysis. Functions of differentially expressed mRNA were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). GO enrichment analysis indicates that 40 known genes and 6 new genes are associated with skeletal muscle development. Additionally, KEGG analysis shows that these genes regulate skeletal muscle development via MAPK, FoxO, Hedgehog, PI3K-Akt, Notch, VEGF and other signaling pathways. Through protein-protein interaction (PPI) and transcription factor prediction (TFP), the action mode of skeletal muscle-related genes was explored. PPI analysis showed that there were stable interactions among 19 proteins, meanwhile, TFP analysis predicted 22 transcription factors such as HMG20B, MYF6, MYOD1 and MYOG, and 12 of the 19 interacting proteins were transcription factors. The regulatory network of ceRNA related to skeletal muscle development was constructed based on the correlation of various RNA expression levels and the targeted binding characteristics with miRNA. The regulatory network included 31 DEms, 59 miRNAs, 667 circRNAs and 224 lncRNAs.conclusion: Overall, the study revealed the role of ceRNA regulatory network in the transformation of skeletal muscle fiber types in Ningxiang pigs, which contributes to the understanding of ceRNA regulatory network in Ningxiang pigs during the skeletal muscle development period.

  • Research Article
  • Cite Count Icon 7
  • 10.1111/jcmm.15778
Characterization of a non-coding RNA-associated ceRNA network in metastatic lung adenocarcinoma.
  • Aug 29, 2020
  • Journal of Cellular and Molecular Medicine
  • Feifei Fan + 13 more

Lung adenocarcinoma (LUAD) is a highly malignant cancer. Although competing endogenous RNA (ceRNA)‐based profiling has been investigated in patients with LUAD, it has not been specifically used to study metastasis in LUAD. We found 130 differentially expressed (DE) lncRNAs, 32 DE miRNAs and 981 DE mRNAs from patients with LUAD in The Cancer Genome Atlas (TCGA) database. We analysed the functions and pathways of 981 DE mRNAs using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Based on the target DE mRNAs and DE lncRNAs of DE miRNAs, we established an lncRNA‐miRNA‐mRNA ceRNA network, comprising 37 DE lncRNAs, 22 DE miRNAs and 212 DE mRNAs. Subsequently, we constructed a protein‐protein interaction network of DE mRNAs in the ceRNA network. Among all, DE RNAs, 5 DE lncRNAs, 5 DE miRNAs and 45 DE mRNAs were confirmed found to be associated with clinical prognosis. Moreover, 3 DE lncRNAs, 4 DE miRNAs and 9 DE mRNAs in the ceRNA network were associated with clinical prognosis. We further screened 3 DE lncRNAs, 3 DE miRNAs and 3 DE mRNAs using clinical samples. These DE lncRNAs, DE miRNAs and DE mRNAs in ceRNA network may serve as independent biomarkers of LUAD metastasis.

  • Research Article
  • Cite Count Icon 2
  • 10.3389/fvets.2022.998796
Characterization of differentially expressed and lipid metabolism-related lncRNA-mRNA interaction networks during the growth of liver tissue through rabbit models
  • Sep 1, 2022
  • Frontiers in Veterinary Science
  • Guoze Wang + 8 more

BackgroundCharacterization the long non-coding RNAs (lncRNAs) and their regulated mRNAs involved in lipid metabolism during liver growth and development is of great value for discovering new genomic biomarkers and therapeutic targets for fatty liver and metabolic syndrome.Materials and methodsLiver samples from sixteen rabbit models during the four growth stages (birth, weaning, sexual maturity, and somatic maturity) were used for RNA-seq and subsequent bioinformatics analyses. Differentially expressed (DE) lncRNAs and mRNAs were screened, and the cis/trans-regulation target mRNAs of DE lncRNAs were predicted. Then the function enrichment analyses of target mRNAs were performed through Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. The target protein interaction (PPI) and lncRNA-mRNA co-expression networks were constructed using string version 11.0 platform and R Stats. Finally, six lncRNAs and six mRNAs were verified taking RT-qPCR.ResultsLiver Oil Red O detection found that the liver showed time-dependent accumulation of lipid droplets. 41,095 lncRNAs, 30,744 mRNAs, and amount to 3,384 DE lncRNAs and 2980 DE mRNAs were identified from 16 cDNA sequencing libraries during the growth of liver. 689 out of all DE lncRNAs corresponded to 440 DE mRNAs by cis-regulation and all DE mRNAs could be regulated by DE lncRNAs by trans-regulation. GO enrichment analysis showed significant enrichment of 892 GO terms, such as protein binding, cytosol, extracellular exsome, nucleoplasm, and oxidation-reduction process. Besides, 52 KEGG pathways were significantly enriched, including 11 pathways of lipid metabolism were found, like Arachidonic acid metabolism, PPAR signaling pathway and Biosynthesis of unsaturated fatty acids. After the low expression DE mRNAs and lncRNAs were excluded, we further obtained the 54 mRNAs were regulated by 249 lncRNAs. 351 interaction pairs were produced among 38 mRNAs and 215 lncRNAs through the co-expression analysis. The PPI network analysis found that 10 mRNAs such as 3β-Hydroxysteroid-Δ24 Reductase (DHCR24), lathosterol 5-desaturase (SC5D), and acetyl-CoA synthetase 2 (ACSS2) were highly interconnected hub protein-coding genes. Except for MSTRG.43041.1, the expression levels of the 11 genes by RT-qPCR were the similar trends to the RNA-seq results.ConclusionThe study revealed lncRNA-mRNA interation networks that regulate lipid metabolism during liver growth, providing potential research targets for the prophylaxis and treatment of related diseases caused by liver lipid metabolism disorders.

  • Research Article
  • Cite Count Icon 11
  • 10.1016/j.psj.2022.102292
Transcriptomic analysis of the thyroid and ovarian stroma reveals key pathways and potential candidate genes associated with egg production in ducks
  • Nov 16, 2022
  • Poultry Science
  • Zhiyu He + 10 more

Transcriptomic analysis of the thyroid and ovarian stroma reveals key pathways and potential candidate genes associated with egg production in ducks

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