Transcriptomics

Dataset Information

7

Involvement of miRNAs in the Regulation of Muscle Wasting during Catabolic Conditions.


ABSTRACT: Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure and in ageing. In fact, excessive proteolysis causes cachexia, accelerates disease progression and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, while the transcriptional control of the atrophy-related genes peaks at 3 days, the changes of miRNA expression maximised at 7 days after denervation. Among the different miRNAs, microRNA-206 and 21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified the transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for the fine-tuning of the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions. To determine which miRNAs are relevant for the atrophic process, we performed miRNA expression profiles of muscles from different atrophic models (starvation, denervation and streptozotocin-induced diabetes). We checked whether there was a common signature of miRNA expression in different atrophying conditions and we found that every catabolic situation require a peculiar pattern of miRNA. We further focus on the condition of denervation and identified the most up-regulated miRNAs in this condition, miRNA-206 and miRNA-21.

ORGANISM(S): Mus musculus  

SUBMITTER: Francesco Chemello   Stefano Cagnin  Matteo Silvestrin  Marco Sandri  Ricardo Soares  Cristiano De Pittà  Gerolamo Lanfranchi 

PROVIDER: E-GEOD-51648 | ArrayExpress | 2014-07-15

SECONDARY ACCESSION(S): GSE51648PRJNA224203

REPOSITORIES: GEO, ArrayExpress

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Publications

Involvement of microRNAs in the regulation of muscle wasting during catabolic conditions.

Soares Ricardo José RJ   Cagnin Stefano S   Chemello Francesco F   Silvestrin Matteo M   Musaro Antonio A   De Pitta Cristiano C   Lanfranchi Gerolamo G   Sandri Marco M  

The Journal of biological chemistry 20140602 32


Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure, and in aging. In fact, excessive proteolysis causes cachexia, accelerates disease progression, and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To unders  ...[more]

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