scholarly journals Global transcriptomic analysis reveals Lnc-ADAMTS9 exerting an essential role in myogenesis through modulating the ERK signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Liqi Wang ◽  
Ting He ◽  
Xin Zhang ◽  
Yubo Wang ◽  
Kai Qiu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Essential Role ◽  
Myogenic Differentiation ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Farm Animals ◽  
Erk Signaling ◽  
Intracellular Ca

Abstract Background Long non-coding RNAs (lncRNAs) are emerging key regulators involved in a variety of biological processes such as cell differentiation and development. The balance between myogenesis and adipogenesis is crucial for skeletal muscle homeostasis in humans and meat quality in farm animals. The present study aimed to reveal the global transcriptomic profiles of adipogenic (Adi-) and myogenic (Myo-) precursors derived from porcine skeletal muscle and identify lncRNAs involved in the modulation of myogenesis homeostasis in porcine skeletal muscle. Results In this study, a total of 655 novel individual lncRNAs including differentially expressed 24 lncRNAs, and 755 differentially expressed mRNAs were identified (fold change ≥2 or ≤ 0.5 and adjusted P < 0.05). Integrated results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis accompanied by the variation of intracellular Ca2+ concentration highlighted Lnc-ADAMTS9 involved in the modulation of myogenesis homeostasis in porcine skeletal muscle. Although Lnc-ADAMTS9 knock-down did not alter the mRNA expression of ADAMTS9, we demonstrated that Lnc-ADAMTS9 can promote myogenic proliferation and myogenic differentiation of myogenic precursors through inhibiting the ERK/MAPK signaling pathway. Conclusion We deciphered a comprehensive catalog of mRNAs and lncRNAs that might be involved in the regulation of myogenesis and adipogenesis homeostasis in the skeletal muscle of pigs. The Lnc-ADAMTS9 exerts an essential role in myogenesis through the ERK signaling pathway.

scholarly journals Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Zhang ◽  
Wenjuan Sun ◽  
Linjuan He ◽  
Liqi Wang ◽  
Kai Qiu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Signaling Pathway ◽  
Myogenic Differentiation ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Methylation Pattern ◽  
Pathway Enrichment Analysis ◽  
Differentiation Potential ◽  
Muscle Homeostasis

Abstract Background Skeletal muscle is a complex and heterogeneous tissue accounting for approximately 40% of body weight. Excessive ectopic lipid accumulation in the muscle fascicle would undermine the integrity of skeletal muscle in humans but endow muscle with marbling-related characteristics in farm animals. Therefore, the balance of myogenesis and adipogenesis is of great significance for skeletal muscle homeostasis. Significant DNA methylation occurs during myogenesis and adipogenesis; however, DNA methylation pattern of myogenic and adipogenic precursors derived from skeletal muscle remains unknown yet. Methods In this study, reduced representation bisulfite sequencing was performed to analyze genome-wide DNA methylation of adipogenic and myogenic precursors derived from the skeletal muscle of neonatal pigs. Integrated analysis of DNA methylation and transcription profiles was further conducted. Based on the results of pathway enrichment analysis, myogenic precursors were transfected with CACNA2D2-overexpression plasmids to explore the function of CACNA2D2 in myogenic differentiation. Results As a result, 11,361 differentially methylated regions mainly located in intergenic region and introns were identified. Furthermore, 153 genes with different DNA methylation and gene expression level between adipogenic and myogenic precursors were characterized. Subsequently, pathway enrichment analysis revealed that DNA methylation programing was involved in the regulation of adipogenic and myogenic differentiation potential through mediating the crosstalk among pathways including focal adhesion, regulation of actin cytoskeleton, MAPK signaling pathway, and calcium signaling pathway. In particular, we characterized a new role of CACNA2D2 in inhibiting myogenic differentiation by suppressing JNK/MAPK signaling pathway. Conclusions This study depicted a comprehensive landmark of DNA methylome of skeletal muscle-derived myogenic and adipogenic precursors, highlighted the critical role of CACNA2D2 in regulating myogenic differentiation, and illustrated the possible regulatory ways of DNA methylation on cell fate commitment and skeletal muscle homeostasis.

scholarly journals CDR1as related miRNA-mRNA networks in differentiating goat skeletal muscle satellite cells

2020 ◽  
Author(s):  
Bismark Kyei ◽  
Li Li ◽  
Liu Yang ◽  
Siyuan Zhan ◽  
Juntao Li ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Satellite Cells ◽  
Muscle Development ◽  
Myogenic Differentiation ◽  
Mapk Signaling ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Muscle Satellite Cells ◽  
Skeletal Muscle Satellite Cells

Abstract Background: Myogenesis is a complex process controlled by several coding and non-coding RNAs (ncRNAs) such as circular RNAs (circRNAs) that well-known function as endogenous microRNAs (miRNAs) sponges. Over the past few years, numerous circRNAs have been known and their roles in biological processes have begun to be understood. Cerebellar Degeneration-Related protein 1 antisense (CDR1as), the most spotlighted circRNA as miR-7 sponge that has been blooming circRNAs’ research for a decade, and can potentially sponge several miRNAs in disease and muscle physiology. Nevertheless, the linear-RNAs-differed character that the acute interventions for circRNAs do not affect miRNAs levels, and has retarded the transcriptome-wide discovery of miRNAs sponged by. Therefore, the purpose of this study was to provide the transcriptomic effect of CDR1as during muscle differentiation.Methods: siCDR1as and siDICER1 were transfected into goat skeletal muscle satellite cells (SMSCs). RNA-seq technology and bioinformatics tools were used to analyze genes that are deregulated by siCDR1as and siDICER1. quantitative PCR was used to verify the expression levels of the differentially expressed mRNAs and miRNAs. Results: Here, to systematically identify miRNAs targeting CDR1as, we employed the critical enzyme DICER1 that governs the biogenesis of miRNAs. The deficiency of either DICER1 or CDR1as inhibited myogenic differentiation of SMSCs, and knockdown of DICER1 decreased the expression of CDR1as. Moreover, we screened for the targeted messenger RNAs (mRNAs) and miRNAs in SMSCs transfected with siDICER1 or siCDR1as respectively and found out that some well-known muscle-related pathways such as phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, Rap1 signaling pathway, and MAPK signaling pathway were enriched in all groups. Further, regarding the miRNAs identified in siDICER1 and siCDR1as together with the sequence complementary information, we identified 11 miRNAs including miR-1, miR-206, and miR-27a-5p which are more likely to be novel targets for CDR1as. Conclusion: In summary, our study provides a perspective on the potential functions and relationship between CDR1as and DICER1 during muscle development.

scholarly journals Circular PPP1R13B RNA Promotes Chicken Skeletal Muscle Satellite Cell Proliferation and Differentiation via Targeting miR-9-5p

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2396
Author(s):  
Xiaoxu Shen ◽  
Yuanhang Wei ◽  
Guishuang You ◽  
Wei Liu ◽  
Felix Kwame Amevor ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Development ◽  
Akt Signaling ◽  
Differentially Expressed ◽  
Farm Animals ◽  
Akt Signaling Pathway ◽  
Skeletal Muscle Development ◽  
Proliferation And Differentiation ◽  
Chicken Skeletal Muscle

Skeletal muscle plays important roles in animal locomotion, metabolism, and meat production in farm animals. Current studies showed that non-coding RNAs, especially the circular RNA (circRNA) play an indispensable role in skeletal muscle development. Our previous study revealed that several differentially expressed circRNAs among fast muscle growing broilers (FMGB) and slow muscle growing layers (SMGL) may regulate muscle development in the chicken. In this study, a novel differentially expressed circPPP1R13B was identified. Molecular mechanism analysis indicated that circPPP1R13B targets miR-9-5p and negatively regulates the expression of miR-9-5p, which was previously reported to be an inhibitor of skeletal muscle development. In addition, circPPP1R13B positively regulated the expression of miR-9-5p target gene insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) and further activated the downstream insulin like growth factors (IGF)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway. The results also showed that the knockdown of circPPP1R13B inhibits chicken skeletal muscle satellite cells (SMSCs) proliferation and differentiation, and the overexpression of circPPP1R13B promotes the proliferation and differentiation of chicken SMSCs. Furthermore, the overexpression of circPPP1R13B could block the inhibitory effect of miR-9-5p on chicken SMSC proliferation and differentiation. In summary, our results suggested that circPPP1R13B promotes chicken SMSC proliferation and differentiation by targeting miR-9-5p and activating IGF/PI3K/AKT signaling pathway.

Identification of Candidate Genetic Markers and a Novel 4-genes Diagnostic Model in Osteoarthritis through Integrating Multiple Microarray Data

2020 ◽  
Vol 23 (8) ◽  
pp. 805-813
Author(s):  
Ai Jiang ◽  
Peng Xu ◽  
Zhenda Zhao ◽  
Qizhao Tan ◽  
Shang Sun ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Microarray Data ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Joint Disease ◽  
Support Vector ◽  
Diagnostic Model ◽  
Data Sets

Background: Osteoarthritis (OA) is a joint disease that leads to a high disability rate and a low quality of life. With the development of modern molecular biology techniques, some key genes and diagnostic markers have been reported. However, the etiology and pathogenesis of OA are still unknown. Objective: To develop a gene signature in OA. Method: In this study, five microarray data sets were integrated to conduct a comprehensive network and pathway analysis of the biological functions of OA related genes, which can provide valuable information and further explore the etiology and pathogenesis of OA. Results and Discussion: Differential expression analysis identified 180 genes with significantly expressed expression in OA. Functional enrichment analysis showed that the up-regulated genes were associated with rheumatoid arthritis (p < 0.01). Down-regulated genes regulate the biological processes of negative regulation of kinase activity and some signaling pathways such as MAPK signaling pathway (p < 0.001) and IL-17 signaling pathway (p < 0.001). In addition, the OA specific protein-protein interaction (PPI) network was constructed based on the differentially expressed genes. The analysis of network topological attributes showed that differentially upregulated VEGFA, MYC, ATF3 and JUN genes were hub genes of the network, which may influence the occurrence and development of OA through regulating cell cycle or apoptosis, and were potential biomarkers of OA. Finally, the support vector machine (SVM) method was used to establish the diagnosis model of OA, which not only had excellent predictive power in internal and external data sets (AUC > 0.9), but also had high predictive performance in different chip platforms (AUC > 0.9) and also had effective ability in blood samples (AUC > 0.8). Conclusion: The 4-genes diagnostic model may be of great help to the early diagnosis and prediction of OA.

scholarly journals MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

2020 ◽  
Author(s):  
Lun Wu ◽  
Ying Wei ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Li-Hua Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Enrichment Analysis ◽  
Gene Chip ◽  
Differentially Expressed ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Therapeutic Benefits ◽  
Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

scholarly journals Comparative analysis of gene expression profiles in differentiated subcutaneous adipocytes between Jiaxing Black and Large White Pigs

2020 ◽  
Author(s):  
Dawei Zhang ◽  
Wenjing Wu ◽  
Xin Huang ◽  
Ke Xu ◽  
Cheng Zheng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Fat Deposition ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Domestic Pig ◽  
Large White ◽  
Pig Breeds

Abstract Background: Chinese domestic pig breeds are reputed for pork quality, but their low ratio of lean-to-fat carcass weight decreases production efficiency. A better understanding of the genetic regulation network of SC fat tissue is necessary for the rational selection of Chinese domestic pig breeds. In the present study, SC adipocytes were isolated from Jiaxing Black pigs (a Chinese indigenous pig breed with redundant SC fat deposition) and Large White pigs (a lean-type pig breed with relatively low SC fat deposition) and the expression profiles of mRNAs and lncRNAs were compared by RNA-seq analysis to identify biomarkers correlated with the differences of SC fat deposition between the two breeds.Results: A total of 3,371 differentially expressed genes (DEGs) and 1,182 differentially expressed lncRNAs (DELs) were identified in SC adipocytes between Jiaxing Black (JX) and Large White (LW) pigs, which included 797 upregulated mRNAs, 2,574 downregulated mRNAs, 461 upregulated lncRNAs and 721 downregulated lncRNAs. Gene Ontology and KEGG pathway analyses revealed that the DEGs and DELs were mainly involved in the immune response, cell fate determination, PI3K-Akt signaling pathway and MAPK signaling pathway, which are known to be related to adipogenesis and lipid metabolism. The expression levels of DEGs and DELs according to the RNA-seq data were verified by quantitative PCR, which showed 81.8% consistency. The differences in MAPK pathway activity between JX and LW pigs was confirmed by western blot analysis, with <100-fold elevated p38 phosphorylation in JX pigs.Conclusions: This study offers a detailed characterization of mRNAs and lncRNAs in fat- and lean-type pig breeds. The activity of the MAPK signaling pathway was found to be associated with subcutaneous adipogenesis. These results greatly enhance our understanding of the molecular mechanisms regulating SC fat deposition in pigs.

scholarly journals Characterization of microRNAs during Embryonic Skeletal Muscle Development in the Shan Ma Duck

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1417
Author(s):  
Chuan Li ◽  
Ting Xiong ◽  
Mingfang Zhou ◽  
Lei Wan ◽  
Suwang Xi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Target Genes ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Meat Production ◽  
Skeletal Muscle Development ◽  
Differentially Expressed Mirnas

Poultry skeletal muscle provides high quality protein for humans. Study of the genetic mechanisms during duck skeletal muscle development contribute to future duck breeding and meat production. In the current study, three breast muscle samples from Shan Ma ducks at embryonic day 13 (E13) and E19 were collected, respectively. We detected microRNA (miRNA) expression using high throughput sequencing following bioinformatic analysis. qRT-PCR validated the reliability of sequencing results. We also identified target prediction results using the luciferase reporter assay. A total of 812 known miRNAs and 279 novel miRNAs were detected in six samples; as a result, 61 up-regulated and 48 down-regulated differentially expressed miRNAs were identified between E13 and E19 (|log2 fold change| ≥ 1 and p ≤ 0.05). Enrichment analysis showed that target genes of the differentially expressed miRNAs were enriched on many muscle development-related gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, especially mitogen-activated protein kinase (MAPK) signaling pathways. An interaction network was constructed using the target genes of the differentially expressed miRNAs. These results complement the current duck miRNA database and offer several miRNA candidates for future studies of skeletal muscle development in the duck.

scholarly journals Proteomic Analysis of Radiation-Induced Acute Liver Damage in a Rabbit Model

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581988950 ◽  
Author(s):  
Lingong Jiang ◽  
Huimin Jia ◽  
Zhicheng Tang ◽  
Xiaofei Zhu ◽  
Yangsen Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Liver Damage ◽  
Rabbit Model ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Differentially Expressed Proteins ◽  
Label Free ◽  
Radiation Induced ◽  
Liver Tissues

Radiation-induced liver damage (RILD) has become a limitation in radiotherapy for hepatocellular carcinoma. We established a rabbit model of RILD by CyberKnife. Electron microscopy analysis revealed obvious nuclear atrophy and disposition of fat in the nucleus after irradiation. We then utilized a mass spectrometry-based label-free relative quantitative proteomics approach to compare global proteomic changes of rabbit liver in response to radiation. In total, 2365 proteins were identified, including 338 proteins that were significantly dysregulated between irradiated and nonirradiated liver tissues. These differentially expressed proteins included USP47, POLR2A, CSTB, MCFD2, and CSNK2A1. Real-time polymerase chain reaction confirmed that USP47 and CABLES1 transcripts were significantly higher in irradiated liver tissues, whereas MCFD2 and CSNK2A1 expressions were significantly reduced. In Clusters of Orthologous Groups of proteins analysis, differentially expressed proteins were annotated and divided into 24 categories, including posttranslational modification, protein turnover, and chaperones. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the enriched pathways in dysregulated proteins included the vascular endothelial growth factors (VEGF) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and the adipocytokine signaling pathway. The identification of proteins and pathways is crucial toward elucidating the radiation response process of the liver, which may facilitate the discovery of novel therapeutic targets.

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