circRNA_0046366 inhibits hepatocellular steatosis by normalization of PPAR signaling

Guo, Xiaoshuang; Sun, Fei; Chen, Jian-Neng; Wang, Yuqin; Pan, Qin; Fan, Jian‐Gao

doi:10.3748/wjg.v24.i3.323

Cited by 79 publications

(69 citation statements)

References 59 publications

(67 reference statements)

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“…PPARα downregulation decreased PPARα-mediated lipid metabolism and led to hepatocellular steatosis, which indicated that circRNA_0046367/miR-34a/PPARα axis might be involved in lipoxidative and reduce hepatic steatosis-inducing HCC ( 96 ). Moreover, other same results have been observed in circRNA_0046366 ( 118 ).…”

Section: Circrnas In Hepatocellular Carcinoma (Hcc)supporting

confidence: 82%

Prospect of Circular RNA in Hepatocellular Carcinoma: A Novel Potential Biomarker and Therapeutic Target

2018

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CircRNA, a kind of tissue specific and covalently closed circular non-coding RNA is very abundant in eukaryocyte. Generally, circRNA is generated by back-splicing of protein-coding genes' pre-mRNA. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Due to the characteristics of poor prognosis and high recurrence, the pathogenesis of HCC is highly concerned by researchers worldwide. Recent studies demonstrated that numerous circRNAs were differentially expressed in HCC tissues and normal liver tissues, which is closely related with the development and prognosis of HCC. However, the mechanism of circRNA in HCC remains unclear. In this review, we summarized the abnormal expressions of circRNAs in HCC, discussed its role, and potential mechanisms, and tried to explore the prospective values of circRNA in the diagnosis, therapy, and prognosis of HCC.

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Section: Circrnas In Hepatocellular Carcinoma (Hcc)supporting

confidence: 82%

Prospect of Circular RNA in Hepatocellular Carcinoma: A Novel Potential Biomarker and Therapeutic Target

2018

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“…4, 5). Although several recent studies have reported that circRNAs play an important role in the stage of simple steatosis 9,32,33 , it is the first time the current study demonstrates that circRNA participates in the progression of NASH and circRNA_002581 may serve as a novel therapeutic target for the treatment of NASH.…”

Section: Discussionmentioning

confidence: 69%

Antagonizing circRNA_002581–miR-122–CPEB1 axis alleviates NASH through restoring PTEN–AMPK–mTOR pathway regulated autophagy

Jin

Zheng

et al. 2020

Cell Death Dis

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Circular RNAs (circRNAs) have been shown to play critical roles in cancer biology, but their functions in nonalcoholic steatohepatitis (NASH) remain unexplored. Full length of circRNA_002581 was amplified and sequenced, followed by RNA immunoprecipitation, RNA-Fluorescence in Situ Hybridization and dual luciferase reporter gene analysis to confirm the existence of the circRNA_002581-miR-122-CPEB1 regulatory axis in vitro. CircRNA_002581 knockdown was used to study its roles in high concentration of free fatty acids-induced NASH-like cell model and a methionine and choline deficiency (MCD) diet-induced NASH mice model. Autophagy flux and related potential PTEN-AMPK-mTOR pathway were tested by western blot. CircRNA_002581 overexpression significantly relieved the inhibitory role of miR-122 on its target CPEB1 by sponging miR-122. CircRNA_002581 knockdown markedly attenuated lipid droplet accumulation, reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), pro-inflammatory cytokines, apoptosis, H 2 O 2 , and increased ATP level in both mice and cellular models of NASH. Mechanistically, circRNA_002581 interference significantly rescue the defective autophagy evidenced by increased autophagosome number, upregulated LC3-II/I level, and decreased p62 level. Further chloroquine-mediated total autophagy inhibition antagonizes the protective effect of circRNA_002581 knockdown. Finally, CPEB1-PTEN-AMPK-mTOR pathway is shown to link the autophagy and circRNA_002581 knockdown-mediated NASH alleviation. CircRNA_002581-miR-122-CPEB1 axis actively participates in the pathogenesis of NASH through PTEN-AMPK-mTOR pathway-related autophagy suppression. Targeting circRNA_002581 is a potential therapeutic strategy for NASH through partial autophagy restoration.

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“…circRNA_0046366 antagonizes miR-34a and normalizes PPARα signaling, leading to the amelioration of liver steatosis in a murine model[ 116 ]. However, a phase I study on the effects of a miR-34 mimic (MRX34) on primary liver cancer and advanced or metastatic cancer with liver involvement (ClinicalTrials.gov Identifier: NCT01829971) was prematurely terminated due to serious immune-related adverse events[ 108 ], highlighting the potential risks of miRNA based-therapies.…”

Section: Role Of Mirnas In Nafldmentioning

confidence: 99%

Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease

Torres

Novo-Veleiro

Manzanedo

et al. 2018

WJG

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple physiological and pathological functions through the modulation of gene expression at the post-transcriptional level. Accumulating evidence has established a role for miRNAs in the development and pathogenesis of liver disease. Specifically, a large number of studies have assessed the role of miRNAs in alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), two diseases that share common underlying mechanisms and pathological characteristics. The purpose of the current review is to summarize and update the body of literature investigating the role of miRNAs in liver disease. In addition, the potential use of miRNAs as biomarkers and/or therapeutic targets is discussed. Among all miRNAs analyzed, miR-34a, miR-122 and miR-155 are most involved in the pathogenesis of NAFLD. Of note, these three miRNAs have also been implicated in ALD, reinforcing a common disease mechanism between these two entities and the pleiotropic effects of specific miRNAs. Currently, no single miRNA or panel of miRNAs has been identified for the detection of, or staging of ALD or NAFLD. While promising results have been shown in murine models, no therapeutic based-miRNA agents have been developed for use in humans with liver disease.

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circRNA_0046366 inhibits hepatocellular steatosis by normalization of PPAR signaling

Cited by 79 publications

References 59 publications

Prospect of Circular RNA in Hepatocellular Carcinoma: A Novel Potential Biomarker and Therapeutic Target

Prospect of Circular RNA in Hepatocellular Carcinoma: A Novel Potential Biomarker and Therapeutic Target

Antagonizing circRNA_002581–miR-122–CPEB1 axis alleviates NASH through restoring PTEN–AMPK–mTOR pathway regulated autophagy

Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease

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