Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data

Yuan, Xinlu; Diao, Jianjun; Du, Anqing; Su, Wen; Zhou, Long; Pan, Yangbin

doi:10.1186/s12967-020-02637-w

Cited by 22 publications

(19 citation statements)

References 21 publications

(23 reference statements)

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“…Therefore, clarification the cellular and molecular mechanism of NASH has become a research hotspot. Over the course of research, it was found that circRNAs might function significantly in progression of NASH, in which a novel type of circRNAs, namely mecciRNAs, have attracted much interest recently [ 14 , 17 , 63 ]. Through bioinformatic analysis and experimental verification, this study has proposed the possibility that mecciRNAs might function as ceRNAs to regulate NASH progression.…”

Section: Discussionmentioning

confidence: 99%

The potential of mecciRNA in hepatic stellate cell to regulate progression of nonalcoholic hepatitis

Liu

Tian

et al. 2022

J Transl Med

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Background Nonalcoholic steatohepatitis (NASH) occupies a substantial proportion of chronic liver disease worldwide, of which pathogenesis needs further research. Recent studies have demonstrated the significant roles of circular RNAs (circRNAs) in NASH, while the function of a novel type of circRNAs, namely mitochondria-encoded circRNAs (mecciRNAs), remains elusive. Therefore, we aimed to investigate their potential to regulate the progression of NASH in this study. Methods GSE134146 was used to screen for differentially expressed mecciRNAs in NASH, while GSE46300 was used to identify NASH-related genes. To establish the mecciRNA-miRNA-mRNA networks, circMINE and miRNet databases were used for predicting downstream targets. Then, consensus clustering analysis was used to determine immune subtypes of NASH. Finally, we successfully validated our findings in vitro (LPS-treated hepatic stellate cells [HSCs]) and in vivo (MCD-diet mice) NASH models. Results We confirmed that circRNomics balance is disrupted in HSCs of NASH, while two mecciRNAs (hsa_circ_0089761 and hsa_circ_0089763) could function as competing for endogenous RNAs (ceRNAs) to regulate fibrosis-related signals. Furthermore, we constructed two ceRNA networks based on mecciRNAs for the first time. Cell and animal NASH models validated our findings that c-MYC and SMAD2/3 were upregulated in HSCs, while THBS1 and p-STAT3 were upregulated in hepatocytes. Moreover, we identified 21 core genes by overlapping the differentially expressed genes (NASH vs. Normal) with mecciRNA-targeted genes. According to their expression profiles, NASH patients could be divided in 2 different clusters, in which proinflammatory signals (TNF and IL-17 pathways) are significantly activated in Cluster 1. Conclusion We successfully established two novel mecciRNA-miRNA-mRNA networks in HSCs and hepatocytes, which were further confirmed by in vitro and in vivo models. Meanwhile, the novel immunotyping model revealed the heterogeneity of NASH, thereby might guiding treatment options. Altogether, our study brought a distinct perspective on the relationship between mecciRNAs and NASH.

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Section: Discussionmentioning

confidence: 99%

The potential of mecciRNA in hepatic stellate cell to regulate progression of nonalcoholic hepatitis

Liu

Tian

et al. 2022

J Transl Med

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“…Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in developed countries, with the fastest growing in the USA, France and the UK. A strong increase is also observed in developing countries and worldwide in general ( 36 , 37 ). In 20–30% of cases, NAFLD slowly progresses to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC).…”

Section: Circrnas’ Involvement In Nafld Pathologymentioning

confidence: 99%

Discussing the role of circular RNA in the pathogenesis of non-alcoholic fatty liver disease and its complications

et al. 2022

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Circular RNAs (circRNAs) are class of non-coding RNA, which are characterized by a covalently closed loop structure. Functionally they can act on cellular physiology, notably by sponging microRNAs (miR), regulating gene expression or interacting with binding protein. To date, circRNAs might represent an interesting, underexploited avenue for new target discovery for therapeutic applications, especially in the liver. The first characteristic of non-alcoholic fatty liver disease (NAFLD) is hepatic cholesterol accumulation, followed by its advanced form of the affection, nonalcoholic steatohepatitis (NASH), due to the occurrence of lobular inflammation, irreversible fibrosis, and in some cases hepatocellular carcinoma (HCC). Therefore, studies have investigated the importance of the dysregulation of circRNAs in the onset of metabolic disorders. In this review, we summarize the potential role of circRNAs in the development of metabolic diseases associated with the liver such as NAFLD or NASH, and their potential to become therapeutic strategies for these pathologies.

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“…circRNA expression profiles are changed in MAFLD, indicating that circular RNA may participate in the development and progression of liver steatosis. 148 , 149 Knockdown of circScd1 in liver cell line AML12 promote hepatic fat content, while overexpression of circScd1 attenuated steatosis, suggesting that circScd1 mediated hepatic steatosis. 150 circRNA_0046366 increased hepatocellular FAO via inhibiting miRNA-34a function, leading to reduced hepatic steatosis.…”

Section: Epigenetics In Mafldmentioning

confidence: 99%

Update on genetics and epigenetics in metabolic associated fatty liver disease

Zhu

Xia

Gao

2022

Therapeutic Advances in Endocrinology

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Nonalcoholic fatty liver disease (NAFLD) is becoming the most frequent chronic liver disease worldwide. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested to replace the nomenclature of NAFLD. For individuals with metabolic dysfunction, multiple NAFLD-related factors also contribute to the development and progression of MAFLD including genetics and epigenetics. The application of genome-wide association study (GWAS) and exome-wide association study (EWAS) uncovers single-nucleotide polymorphisms (SNPs) in MAFLD. In addition to the classic SNPs in PNPLA3, TM6SF2, and GCKR, some new SNPs have been found recently to contribute to the pathogenesis of liver steatosis. Epigenetic factors involving DNA methylation, histone modifications, non-coding RNAs regulations, and RNA methylation also play a critical role in MAFLD. DNA methylation is the most reported epigenetic modification. Developing a non-invasion biomarker to distinguish metabolic steatohepatitis (MASH) or liver fibrosis is ongoing. In this review, we summarized and discussed the latest progress in genetic and epigenetic factors of NAFLD/MAFLD, in order to provide potential clues for MAFLD treatment.

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Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data

Cited by 22 publications

References 21 publications

The potential of mecciRNA in hepatic stellate cell to regulate progression of nonalcoholic hepatitis

The potential of mecciRNA in hepatic stellate cell to regulate progression of nonalcoholic hepatitis

Discussing the role of circular RNA in the pathogenesis of non-alcoholic fatty liver disease and its complications

Update on genetics and epigenetics in metabolic associated fatty liver disease

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