Genome-Wide Profiling of miRNA-mRNA regulatory network in Skeletal Muscle with Aging
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55165 | GEO | 2014/08/08
SECONDARY ACCESSION(S): PRJNA238655
REPOSITORIES: GEO
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Project description:Skeletal muscle degenerates progressively, losing mass (sarcopenia) over time, which leads to reduced physical ability and often results in secondary diseases such as diabetes and obesity. The regulation of gene expression by microRNAs is a key event in muscle development and disease. To understand genome?wide changes in microRNAs and mRNAs during muscle aging, we sequenced microRNAs and mRNAs from mouse gastrocnemius muscles at two different ages (6 and 24 months). Thirty?four microRNAs (15 up?regulated and 19 down?regulated) were differentially expressed with age, including the microRNAs miR?206 and ?434, which were differentially expressed in aged muscle in previous studies. Interestingly, eight microRNAs in a microRNA cluster at the imprinted Dlk1?Dio3 locus on chromosome 12 were coordinately down?regulated. In addition, sixteen novel microRNAs were identified. Integrative analysis of microRNA and mRNA expression revealed that microRNAs may contribute to muscle aging through the positive regulation of transcription, metabolic processes, and kinase activity. Many of the age?related microRNAs have been implicated in human muscular diseases. We suggest that genome?wide microRNA profiling will expand our knowledge of microRNA function in the muscle aging process.
| S-EPMC4153621 | biostudies-literature
Project description:Skeletal muscle degenerates progressively, loses mass (sarcopenia) along in years, and leads to reduced physical ability, often causing secondary diseases such as diabetes and obesity. It is known that regulation of gene expression by microRNAs is a key event in muscle development and disease. To understand genome-wide changes in microRNAs and mRNAs during muscle aging, we sequenced microRNAs as well as mRNAs from mouse gastrocnemius muscles at two different ages (6 versus 24-month-old). Thirty-four microRNAs (15 up-regulated and 19 down-regulated) were differentially expressed with age among which were microRNAs such as miR-206 or -434 which were differentially expressed in aged muscle in previous studies. Interestingly, seven microRNAs in a microRNA cluster at imprinted Dlk1-Dio3 locus on chromosome 12 were coordinately down-regulated. In addition, sixteen novel microRNAs were identified. Integrative analysis of microRNA and mRNA expression revealed that microRNAs contribute to muscle aging possibly through the positive regulation of transcription, metabolic process, and kinase activity. Many of the age-related microRNAs were implicated in human muscular diseases. We suggest that genome-wide microRNA profiling helps to expand our knowledge of microRNA function in the muscle aging process.
2014-08-08 | GSE55164 | GEO
Project description:Skeletal muscle degenerates progressively, loses mass (sarcopenia) along in years, and leads to reduced physical ability, often causing secondary diseases such as diabetes and obesity. It is known that regulation of gene expression by microRNAs is a key event in muscle development and disease. To understand genome-wide changes in microRNAs and mRNAs during muscle aging, we sequenced microRNAs as well as mRNAs from mouse gastrocnemius muscles at two different ages (6 versus 24-month-old). Thirty-four microRNAs (15 up-regulated and 19 down-regulated) were differentially expressed with age among which were microRNAs such as miR-206 or -434 which were differentially expressed in aged muscle in previous studies. Interestingly, seven microRNAs in a microRNA cluster at imprinted Dlk1-Dio3 locus on chromosome 12 were coordinately down-regulated. In addition, sixteen novel microRNAs were identified. Integrative analysis of microRNA and mRNA expression revealed that microRNAs contribute to muscle aging possibly through the positive regulation of transcription, metabolic process, and kinase activity. Many of the age-related microRNAs were implicated in human muscular diseases. We suggest that genome-wide microRNA profiling helps to expand our knowledge of microRNA function in the muscle aging process. miRNA profiles of gastrocnemius muscle tissues (n=10) were generated by deep sequencing using Illumina Hiseq-2000
2014-08-08 | E-GEOD-55164 | biostudies-arrayexpress
Project description:Skeletal muscle degenerates progressively, loses mass (sarcopenia) along in years, and leads to reduced physical ability, often causing secondary diseases such as diabetes and obesity. It is known that regulation of gene expression by microRNAs is a key event in muscle development and disease. To understand genome-wide changes in microRNAs and mRNAs during muscle aging, we sequenced microRNAs as well as mRNAs from mouse gastrocnemius muscles at two different ages (6 versus 24-month-old). Thirty-four microRNAs (15 up-regulated and 19 down-regulated) were differentially expressed with age among which were microRNAs such as miR-206 or -434 which were differentially expressed in aged muscle in previous studies. Interestingly, seven microRNAs in a microRNA cluster at imprinted Dlk1-Dio3 locus on chromosome 12 were coordinately down-regulated. In addition, sixteen novel microRNAs were identified. Integrative analysis of microRNA and mRNA expression revealed that microRNAs contribute to muscle aging possibly through the positive regulation of transcription, metabolic process, and kinase activity. Many of the age-related microRNAs were implicated in human muscular diseases. We suggest that genome-wide microRNA profiling helps to expand our knowledge of microRNA function in the muscle aging process.
2014-08-08 | GSE55163 | GEO
Project description:Skeletal muscle degenerates progressively, loses mass (sarcopenia) along in years, and leads to reduced physical ability, often causing secondary diseases such as diabetes and obesity. It is known that regulation of gene expression by microRNAs is a key event in muscle development and disease. To understand genome-wide changes in microRNAs and mRNAs during muscle aging, we sequenced microRNAs as well as mRNAs from mouse gastrocnemius muscles at two different ages (6 versus 24-month-old). Thirty-four microRNAs (15 up-regulated and 19 down-regulated) were differentially expressed with age among which were microRNAs such as miR-206 or -434 which were differentially expressed in aged muscle in previous studies. Interestingly, seven microRNAs in a microRNA cluster at imprinted Dlk1-Dio3 locus on chromosome 12 were coordinately down-regulated. In addition, sixteen novel microRNAs were identified. Integrative analysis of microRNA and mRNA expression revealed that microRNAs contribute to muscle aging possibly through the positive regulation of transcription, metabolic process, and kinase activity. Many of the age-related microRNAs were implicated in human muscular diseases. We suggest that genome-wide microRNA profiling helps to expand our knowledge of microRNA function in the muscle aging process. mRNA profiles of gastrocnemius muscle tissues (n=10) were generated by deep sequencing using Illumina Hiseq-2000
2014-08-08 | E-GEOD-55163 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-08 | E-GEOD-55165 | biostudies-arrayexpress
Project description:Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-? pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF-? (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs found to be downregulated in CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal-7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p (R(2)=0.56, P=0.0001) and hsa-let-7b-5p (R(2)=0.19, P=0.02) expression was observed in the same samples, corroborating the belief of EZH2 being a bona fide target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to significant reduction in trimethylated histone H3 on lysine 27 (H3K27) methylation, marked reduction in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks as potential therapeutic strategy for CRC.
| S-EPMC4669754 | biostudies-literature
Project description:Age-associated loss of muscle mass and function is a major cause of morbidity and mortality in the elderly adults. Muscular atrophy can also be induced by disuse associated with long-term bed rest or disease. Although miRNAs regulate muscle growth, regeneration, and aging, their potential role in acute muscle atrophy is poorly understood. Furthermore, alterations in circulating miRNA levels have been shown to occur during aging but their potential as noninvasive biomarkers for muscle atrophy remains largely unexplored. Here, we report comprehensive miRNA expression profiles by miRNA-seq analysis in tibialis anterior muscle and serum of a disuse-induced atrophy mouse model, mimicking the acute atrophy following long-term bed rest, as compared to those of young and old mice. Comparative analysis and validation studies have revealed that miR-455-3p was significantly decreased in muscle of both induced-atrophy model and old mice, whereas miR-434-3p was decreased in both serum and muscle of old mice, as compared to young mice. Furthermore, upregulation of miR-455-3p in fully differentiated C2C12 myoblasts induced a hypertrophic phenotype. These results suggest that deregulation of miR-455-3p may play a functional role in muscle atrophy and miR-434-3p could be a candidate serum biomarker of muscle aging.
| S-EPMC5861915 | biostudies-literature
Project description:BACKGROUND Our study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) which can serve as potential biomarkers for diagnosis and therapy of Alzheimer's disease (AD). MATERIAL AND METHODS We performed miRNA and mRNA integrated analysis (MMIA) to identify DEGs and DEmiRNAs of AD. The AD-specific DEmiRNAs-targets interaction network was contrasted. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Q-RT-PCR was used to verify the expression of selected DEGs and DEmiRNAs. RESULTS We conducted MMIA of AD based on 1 miRNA dataset and 3 mRNA datasets derived from the Gene Expression Omnibus (GEO) database; 1759 DEGs and 12 DEmiRNAs were obtained. DEGs of AD were significantly enriched in Huntington's disease and AD. LRP1, CDK5R1, PLCb2, NDUFA4, and DLG4 were 5 DEGs regulated by 4 DEmiRNAs, including miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. These 4 miRNAs were the top 4 miRNAs covering most DEGs. According to the qRT-PCR results, the expression of PLC?2, NDUFA4, DLG4, miR-107, and miR-103a-3p was consistent with our integrated analysis. CONCLUSIONS We concluded that LRP1, CDK5R1, PLC?2, NDUFA4, and DLG4 may play a role in AD regulated by miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. Our findings will contribute to identification of biomarkers and new strategies for drug design for AD treatment.
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Project description:Growing evidence has demonstrated the emerging role of long non-coding RNA as competitive endogenous RNA (ceRNA) in regulating skeletal muscle development. However, the mechanism of ceRNA regulated by lncRNA in pigeon skeletal muscle development remains unclear. To reveal the function and regulatory mechanisms of lncRNA, we first analyzed the expression profiles of lncRNA, microRNA (miRNA), and mRNA during the development of pigeon skeletal muscle using high-throughput sequencing. We then constructed a lncRNA-miRNA-mRNA ceRNA network based on differentially expressed (DE) lncRNAs, miRNAs, and mRNAs according to the ceRNA hypothesis. Functional enrichment and short time-series expression miner (STEM) analysis were performed to explore the function of the ceRNA network. Hub lncRNA-miRNA-mRNA interactions were identified by connectivity degree and validated using dual-luciferase activity assay. The results showed that a total of 1625 DE lncRNAs, 11,311 DE mRNAs, and 573 DE miRNAs were identified. A ceRNA network containing 9120 lncRNA-miRNA-mRNA interactions was constructed. STEM analysis indicated that the function of the lncRNA-associated ceRNA network might be developmental specific. Functional enrichment analysis identified potential pathways regulating pigeon skeletal muscle development, such as cell cycle and MAPK signaling. Based on the connectivity degree, lncRNAs TCONS_00066712, TCONS_00026594, TCONS_00001557, TCONS_00001553, and TCONS_00003307 were identified as hub genes in the ceRNA network. lncRNA TCONS_00026594 might regulate the FSHD region gene 1 (FRG1)/ SRC proto-oncogene, non-receptor tyrosine kinase (SRC) by sponge adsorption of cli-miR-1a-3p to affect the development of pigeon skeletal muscle. Our findings provide a data basis for in-depth elucidation of the lncRNA-associated ceRNA mechanism underlying pigeon skeletal muscle development.
| S-EPMC8625974 | biostudies-literature