Dataset Information

CircFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression.

ABSTRACT: Although many circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been discovered in adipocytes, their precise functions and molecular mechanisms remain poorly understood. Based on existing circRNA and lncRNA sequencing data of bovine adipocytes, we screened for the differential expression of circFLT1 and lncCCPG1 in preadipocytes and adipocytes and further analyzed their function and regulation during adipogenesis. The overexpression of circFLT1 and lncCCPG1 together facilitated adipocyte differentiation and suppressed proliferation. Computationally, the RNA hybrid showed that circFLT1 and lncCCPG1 had multiple potential binding sites with miR-93. Additionally, luciferase reporting experiments verified that circFLT1 and lncCCPG1 may interact with miR-93. We also demonstrated that overexpressed miR-93 effectively suppresses the expression of lncSLC30A9. Signaling pathway enrichment analysis, luciferase activity assay, and expression analysis revealed that lncSLC30A9 inhibits proliferation by inhibiting the expression of AKT protein and promotes differentiation by recruiting the FOS protein to the promoter of peroxisome proliferator-activated receptor gamma (PPARG). In sum, our results elucidate the regulatory mechanisms of circFLT1 and lncCCPG1 as miR-93 sponges in bovine adipocytes.

SUBMITTER: Kang Z

PROVIDER: S-EPMC7554329 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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circFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression.

Kang Zihong Z Zhang Sihuang S Jiang Enhui E Wang Xinyu X Wang Zhen Z Chen Hong H Lan Xianyong X

Molecular therapy. Nucleic acids 20200916

Although many circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been discovered in adipocytes, their precise functions and molecular mechanisms remain poorly understood. Based on existing circRNA and lncRNA sequencing data of bovine adipocytes, we screened for the differential expression of circFLT1 and lncCCPG1 in preadipocytes and adipocytes and further analyzed their function and regulation during adipogenesis. The overexpression of circFLT1 and lncCCPG1 ...[more]

PMID: 33230451

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Project description:Background/objectivesMyostatin (Mstn) has a pivotal role in glucose and lipid metabolism. Mstn deficiency leads to the increased browning of white adipose tissue (WAT), which results in the increased energy expenditure and protection against diet-induced obesity and insulin resistance. In this study, we investigated the molecular mechanism(s) through which Mstn regulates browning of white adipocytes.MethodsQuantitative molecular analyses were performed to assess Mstn regulation of miR-34a and Fndc5 expression. miR-34a was overexpressed and repressed to investigate miR-34a regulation of Fndc5. Luciferase reporter analysis verified direct binding between miR-34a and the Fndc5 3'-untranslated region (UTR). The browning phenotype of Mstn-/- adipocytes was assessed through the analysis of brown fat marker gene expression, mitochondrial function and infrared thermography. The role of miR-34a and Fndc5 in this browning phenotype was verified through antibody-mediated neutralization of FNDC5, knockdown of Fndc5 by small interfering RNA and through miR-34a gain-of-function and loss-of-function experiments.ResultsMstn treatment of myoblasts inhibited Fndc5 expression, whereas the loss of Mstn increased Fndc5 levels in muscles and in circulation. Mstn inhibition of Fndc5 is miR-34a dependent. Mstn treatment of C2C12 myoblasts upregulated miR-34a expression, whereas reduced miR-34a expression was noted in Mstn-/- muscle and WAT. Subsequent overexpression of miR-34a inhibited Fndc5 expression, whereas blockade of miR-34a increased Fndc5 expression in myoblasts. Reporter analysis revealed that miR-34a directly suppresses Fndc5 expression through a miR-34a-specific binding site within the Fndc5 3'UTR. Importantly, Mstn-mediated inhibition of Fndc5 was blocked upon miR-34a inhibition. Mstn-/- adipocytes showed reduced miR-34a, enhanced Fndc5 expression and increased thermogenic gene expression, which was reversed upon either neutralization of Fndc5 or Fndc5 knockdown. In agreement, Mstn-/- adipocytes have increased mitochondria, improved mitochondrial function and increased heat production.ConclusionsMstn regulates Fndc5/Irisin expression and secretion through a novel miR-34a-dependent post-transcriptional mechanism. Loss of Mstn in mice leads to the increased Fndc5/Irisin expression, which contributes to the browning of white adipocytes.

Dataset Information

CircFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression.

Publications

circFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression.

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