MicroRNAs-Dependent Regulation of PPARs in Metabolic Diseases and Cancers.

Dorothea Portius,Cyril Sobolewski,Michelangelo Foti

doi:10.1155/2017/7058424

Dorothea Portius, Cyril Sobolewski + Show 1 more

Open Access

https://doi.org/10.1155/2017/7058424

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Journal: Ppar Research	Publication Date: Jan 1, 2017
Citations: 55	License type: CC BY 4.0

Affiliation: University of Geneva

Abstract

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-dependent nuclear receptors, which control the transcription of genes involved in energy homeostasis and inflammation and cell proliferation/differentiation. Alterations of PPARs' expression and/or activity are commonly associated with metabolic disorders occurring with obesity, type 2 diabetes, and fatty liver disease, as well as with inflammation and cancer. Emerging evidence now indicates that microRNAs (miRNAs), a family of small noncoding RNAs, which fine-tune gene expression, play a significant role in the pathophysiological mechanisms regulating the expression and activity of PPARs. Herein, the regulation of PPARs by miRNAs is reviewed in the context of metabolic disorders, inflammation, and cancer. The reciprocal control of miRNAs expression by PPARs, as well as the therapeutic potential of modulating PPAR expression/activity by pharmacological compounds targeting miRNA, is also discussed.

Highlights

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors involved in various biological functions but with a prominent role in metabolic homeostasis of carbohydrates and lipids [1]
Upregulation of miR-27b in human macrophages upon LPS exposure was demonstrated to directly target PPARγ and to elicit a Th1 differentiation [49]. These findings suggest that miR-27bdependent downregulation of PPARγ may represent a key process in macrophage polarization, whether miR-27b controls M2 macrophage activation via PPARγ was not investigated
The pivotal role of abnormal PPARs signaling in the development and the progression of various pathologies including metabolic diseases, inflammation, and cancer is well established

Summary

Introduction

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors involved in various biological functions but with a prominent role in metabolic homeostasis of carbohydrates and lipids [1]. PPARβ/δ contributes to adaptive thermogenesis by inducing the expression of UCP-1 and UCP-3 [81, 82] and to β-oxidation, by upregulating several genes involved in this process (e.g., long chain acyl-CoA synthetase, Acyl-CoA oxidase) In addition to these well established roles of PPARβ/δ, this isoform was further implicated in the regulation of multiple other cellular processes including developmental aspects, vascular function, and anti-inflammatory responses [4, 6, 44, 79]. MiR-27b-dependent downregulation of PPARγ promotes cell proliferation in HCC, it may lead to opposite effects in other cancers [7, 51, 92– 95] This is the case in the SK-N-AS neuroblastoma cells and derived mouse xenografts, where miR-27b was shown to repress PPARγ expression resulting in a decreased inflammatory response and tumor growth [51, 105, 106]

Indirect Regulation of PPARs by miRNAs

Findings

Conclusion