ena-STUDY-Centrum Medyczne Ksztalcenia Podyplomowego-22-03-2017-08:25:20:245-20
Ectopic overexpression of MCPIP1 impairs adipogenesis by modulating microRNAs.
Adipogenesis, process of fat tissue formation, requires activity of transcription factors, growth factors and others molecules, including miRNAs. Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) has been shown to be an important regulator of adipocyte differentiation and its forced expression impairs adipogenesis. MCPIP1 exerts its anti-adipogenic role by a direct degradation of the C/EBPß transcript. Moreover, MCPIP1 has been identified as a broad suppressor of the miRNA biogenesis. We expect that besides C/EBPß, miRNAs essential for adipogenesis are under the direct control of MCPIP1. Using Next-Generation Sequencing we compared miRNA expression profile in 3T3-L1 adipocytes overexpressing MCPIP1 and control cells. We identified 58 differentially expressed miRNAs, of which 30 were down- and 28 up-regulated in MCPIP1-overexpressing adipocytes. To define the adipogenic-related miRNAs which expression is dependent on MCPIP1, we examined 24 miRNAs with significantly decreased expression level (P-value <0.01) at least 1.5-times. By Q-RT-PCR we confirmed a decreased expression of 3 miRNAs (mir-152-3p, mir-26b and mir-30e) which function in adipogenesis was known and 2 miRNAs (mir-9-3p and mir-32) which expression has never been linked with adipocyte biology before. Furthermore, for the functional annotation we performed target predictions analysis of co-expressed miRNAs. We identified MAPK signaling pathway as the most significantly modulated by investigated down-regulated miRNAs. Moreover, for selected miRNAs we evaluated their target genes by demonstrating increase of their expression on the mRNA level in Q-RT-PCR analysis. Our data indicate an impact of adipocyte-related miRNAs in adipocyte biology and may help to explain the negative role of MCPIP1 in adipocyte differentiation.
Adipogenesis, process of fat tissue formation, requires activity of transcription factors, growth factors and others molecules, including miRNAs. Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) has been shown to be an important regulator of adipocyte differentiation and its forced expression impairs adipogenesis. MCPIP1 exerts its anti-adipogenic role by a direct degradation of the C/EBPß transcript. Moreover, MCPIP1 has been identified as a broad suppressor of the miRNA biogenesis. We expect that besides C/EBPß, miRNAs essential for adipogenesis are under the direct control of MCPIP1. Using Next-Generation Sequencing we compared miRNA expression profile in 3T3-L1 adipocytes overexpressing MCPIP1 and control cells. We identified 58 differentially expressed miRNAs, of which 30 were down- and 28 up-regulated in MCPIP1-overexpressing adipocytes. To define the adipogenic-related miRNAs which expression is dependent on MCPIP1, we examined 24 miRNAs with significantly decreased expression level (P-value <0.01) at least 1.5-times. By Q-RT-PCR we confirmed a decreased expression of 3 miRNAs (mir-152-3p, mir-26b and mir-30e) which function in adipogenesis was known and 2 miRNAs (mir-9-3p and mir-32) which expression has never been linked with adipocyte biology before. Furthermore, for the functional annotation we performed target predictions analysis of co-expressed miRNAs. We identified MAPK signaling pathway as the most significantly modulated by investigated down-regulated miRNAs. Moreover, for selected miRNAs we evaluated their target genes by demonstrating increase of their expression on the mRNA level in Q-RT-PCR analysis. Our data indicate an impact of adipocyte-related miRNAs in adipocyte biology and may help to explain the negative role of MCPIP1 in adipocyte differentiation.