Relationship between Telomere Maintenance and Liver Disease

Barnard, Abbey; Moch, Ashley; Saab, Sammy

doi:10.5009/gnl18081

Cited by 22 publications

(15 citation statements)

References 33 publications

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“…With the overexpression of hsa_circ_0004018, the expression of TEP1 was upregulated ( Figure 6E). The telomeres are known to shorten with age and associated with increased incidence of chronic liver disease [24]. As a component of the telomerase, TEP1 can contribute to the maintenance of telomeres [25].…”

Section: Agingmentioning

confidence: 99%

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hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis

Song

et al. 2020

Aging

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Efforts have been made in the prevention and treatment of liver fibrosis. The inhibition or depletion of the hepatic stellate cells (HSCs) has been considered as a potential approach. Recently, there are numbers of studies about the role of the circular RNA in the disease progression. However, the role of circular RNA in the regulation of HSCs and the progression of liver fibrosis remained elusive. In this study, we constructed a CCl4-induced liver fibrosis mouse model and overexpressed hsa_circ_0004018 in HSCs. Then, salvianolic acid B was used to treat HSCs in vitro. We found that hsa_circ_0004018 is downregulated in liver fibrogenesis. Luciferase reporter assay was performed to verify the interaction of hsa_circ_0004018, hsa-miR-660-3p and TEP1. It showed that hsa_circ_0004018 may act as a sponge of hsa-miR-660-3p, which can target and downregulate the expression of TEP1. hsa_circ_0004018 expressing lentivirus was used to investigate the in-vivo function of hsa_circ_0004018 in CCl4-induced liver fibrosis mice. We also reveal that the hsa_circ_0004018/hsa-miR-660-3p/TEP1 axis contributes to the proliferation and activation of HSCs. In addition, the overexpression of hsa_circ_0004018 alleviated the progression of liver fibrosis. In conclusion, our study highlights hsa_circ_0004018 as a potential biomarker and therapeutic target for liver fibrosis.

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Section: Agingmentioning

confidence: 99%

“…As a component of the telomerase, TEP1 can contribute to the maintenance of telomeres [25]. A number of studies have been reported that the hepatic or immune cell telomeres may associate with liver fibrosis [24]. However, the function of TEP1 in the HSCs and its role in liver fibrosis remained unknown before.…”

Section: Agingmentioning

confidence: 99%

hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis

Song

et al. 2020

Aging

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“…Many circRNAs have been found to suppress the activation of HSCs. Telomeraseassociated protein 1 (TEP1), a component of telomerase and target of hsa-miR-660-3p [102], plays a key role in the development of liver fibrosis and cirrhosis [103]. Overexpression of hsa_circ_0004018, a sponge of hsa-miR-660-3p, increases the expression of TEP1 and significantly suppresses the proliferation and activation of HSCs [104].…”

Section: Liver Fibrosis/cirrhosismentioning

confidence: 99%

Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases

Zeng

Yuan

Cai

et al. 2021

Cells

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Circular RNA (circRNA) is a type of non-coding RNA characterized by a covalently closed continuous loop. CircRNA is generated by pre-mRNA through back-splicing and is probably cleared up by extracellular vesicles. CircRNAs play a pivotal role in the epigenetic regulation of gene expression at transcriptional and post-transcriptional levels. Recently, circRNAs have been demonstrated to be involved in the regulation of liver homeostasis and diseases. However, the epigenetic role and underlying mechanisms of circRNAs in chronic liver diseases remain unclear. This review discussed the role of circRNAs in non-neoplastic chronic liver diseases, including alcoholic liver disease (ALD), metabolic-associated fatty liver disease (MAFLD), viral hepatitis, liver injury and regeneration, liver cirrhosis, and autoimmune liver disease. The review also highlighted that further efforts are urgently needed to develop circRNAs as novel diagnostics and therapeutics for chronic liver diseases.

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“…Interestingly, cancer cells acquire the ability to maintain telomere during tumor progression as an increased telomerase activity is found in 90% of human cancers [32,33]. How telomere shortening, which causes genetic instability and thus promotes transformation in exhausted hepatocytes, is recovered in cancer cells is currently a topic of intensive research [34,35].…”

Section: Genetic Instability In Fibrotic Livermentioning

confidence: 99%

High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway

Moon

Cho

Shin

et al. 2019

IJMS

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Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, making up about 80% of cases. Liver fibrosis and its end-stage disease, cirrhosis, are major risk factors for HCC. A fibrotic liver typically shows persistent hepatocyte death and compensatory regeneration, chronic inflammation, and an increase in reactive oxygen species, which collaboratively create a tumor-promoting microenvironment via inducing genetic alterations and chromosomal instability, and activating various oncogenic molecular signaling pathways. In this article, we review recent advances in fields of liver fibrosis and carcinogenesis, and consider several molecular signaling pathways that promote hepato-carcinogenesis under the microenvironment of liver fibrosis. In particular, we pay attention to emerging roles of the Hippo-YAP/TAZ signaling pathway in stromal activation, hepatic fibrosis, and liver cancer.

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Relationship between Telomere Maintenance and Liver Disease

Cited by 22 publications

References 33 publications

hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis

hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis

Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases

High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway

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