circRNA_0046367 Prevents Hepatoxicity of Lipid Peroxidation: An Inhibitory Role against Hepatic Steatosis

Autor: Fang Sun, Jian-Gao Fan, Yu-Qin Wang, Qin Pan, Xing-Ya Guo, Jian-Neng Chen
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Oxidative Medicine and Cellular Longevity
Oxidative Medicine and Cellular Longevity, Vol 2017 (2017)
ISSN: 1942-0900
DOI: 10.1155/2017/3960197
Popis: Hepatic steatosis reflects the miRNA-related pathological disorder with triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma. Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a that underlies hepatic steatosis. In contrast to its expression loss during the hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization abolished miR-34a’s inhibitory effect on peroxisome proliferator-activated receptorα(PPARα) via blocking the miRNA/mRNA interaction with miRNA response elements (MREs). PPARαrestoration led to the transcriptional activation of genes associated with lipid metabolism, including carnitine palmitoyltransferase 2 (CPT2) and acyl-CoA binding domain containing 3 (ACBD3), and then resulted in the steatosis resolution. Hepatotoxicity of steatosis-related lipid peroxidation, being characterized by mitochondrial dysfunction, growth arrest, and apoptosis, is resultantly prevented after the circRNA_0046367 administration. These findings indicate a circRNA_0046367/miR-34a/PPARαregulatory system underlying hepatic steatosis. Normalized expression of circRNA_0046367 may ameliorate the lipoxidative stress on the basis of steatosis attenuation. circRNA_0046367, therefore, is suggested to be potential approach to the therapy of lipid peroxidative damage.
Databáze: OpenAIRE
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