Mutual induction of transcription factorPPARγ and microRNAs miR‐145 and miR‐329

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that are known to control mRNA translation. Most miRNAs are transcribed from specific genes with well-defined promoters located throughout the genome. The mechanisms that control miRNA expression under normal and pathological conditions are not yet understood clearly. Peroxisome proliferator-activated receptor (PPAR) c is a ligand-activated transcription factor that is extensively distributed in the CNS. PPARc activation induces neuroprotection by modulating genes that contain peroxisome proliferator response elements (PPREs) in their promoters. We presently evaluated if PPARc modulates miRNA expression. When adult rats were treated with PPARc agonist rosiglitazone, expression of 28 miRNAs altered significantly (12 up-and 16 down-regulated; 3-119 fold) in the cerebral cortex compared to vehicle-treated controls. In silico analysis showed 1-5 PPREs in the putative promoter regions (within 1 Kb upstream of the transcription start site) of these miRNA genes. Cotransfection with a PPARc constitutively expressing vector significantly induced the miR-145 and miR-329 promoter vectors (each have four PPREs), which was curtailed by point mutations of PPREs in their promoters. Interestingly, the PPARc promoter has binding sites for both these miRNAs and transfection with miR-329 mimic and miR-145 mimic induced the PPARc expression. Thus, these studies show a cyclical induction of miRNAs and PPARc, indicating that the pleiotropic beneficial effects of PPARc agonists might be modulated in part by miRNAs and their down-stream mRNAs.

MiR‐145 Regulates Lipogenesis in Goat Mammary Cells Via Targeting INSIG1 and Epigenetic Regulation of Lipid‐Related Genes

“…In addition, the up‐regulation of PPARG , LXRA , and SREBF1 increased the content of UFA by regulating the expression level of SCD1 (Wang et al, ; Shi et al, ; Xu et al, ). Therefore, the data highlighting that cells treated with Ad‐PPARG, Ad‐SREBF1, and Ad‐LXRA had greater expression of miR‐145 and that miR‐145 overexpression altered PPARG , SREBF1 , and LXRA expression profiles is consistent with a previous study revealing that there is a cyclical potentiation of the down‐stream actions of PPARG as the miR‐145 are induced by PPARG and they, in turn, induce more PPARG expression (Dharap et al, ). Therefore, the links between the miR‐145 and transcription factors likely have functional relevance and underscore that miR‐145 could play a crucial role in the regulation of milk fat synthesis.…”

Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia

“…23–30 On the other hand inhibiting miRNAs induced after a stroke like miR-181a, miR-479, let-7f and miR-145 were also shown to protect the brain after focal ischemia in rodents. 3,8,31–33 …”

rSjP40 protein promotes PPARγ expression in LX‐2 cells through microRNA‐27b

“…Recent studies show that the miRNAs not only can bind to 39-UTRs of mRNAs to prevent mRNAs translation but also bind to the promoters of mRNAs to induce mRNAs expression. For example, miR-145 and miR-329 are reported to bind to PPARg promoter to transactivate PPARg expression in PC12 cells (20). PPARg is also reported to be involved in liver fibrosis.…”