LncRNA and circRNA in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review

Zeng, Qingmin; Liu, Changhai; Wu, Dongbo; Zhang, Nannan; Tang, Hong

doi:10.3390/biom13030560

Cited by 16 publications

(16 citation statements)

References 67 publications

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“…The above notions extensively illustrate the urgent need for accurate, noninvasive tests (NITs) to diagnose NASH. Blood-based biomarkers (“wet test”) and imaging techniques (“dry tests”) have been recently discussed in comprehensive systematic reviews [ 140 , 141 , 142 , 143 , 144 ]. An increasing number of NITs have been developed for the diagnosis of NAFLD, definite NASH, or at-risk NASH, as well as clinically significant or advanced fibrosis.…”

Section: Pitfalls In Endpoints In Nash Clinical Trialsmentioning

confidence: 99%

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

Lonardo,

Ballestri,

Mantovani

et al. 2024

Metabolites

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This narrative review aims to illustrate the notion that nonalcoholic steatohepatitis (NASH), recently renamed metabolic dysfunction-associated steatohepatitis (MASH), is a systemic metabolic disorder featuring both adverse hepatic and extrahepatic outcomes. In recent years, several NASH trials have failed to identify effective pharmacological treatments and, therefore, lifestyle changes are the cornerstone of therapy for NASH. with this context, we analyze the epidemiological burden of NASH and the possible pathogenetic factors involved. These include genetic factors, insulin resistance, lipotoxicity, immuno-thrombosis, oxidative stress, reprogramming of hepatic metabolism, and hypoxia, all of which eventually culminate in low-grade chronic inflammation and increased risk of fibrosis progression. The possible explanations underlying the failure of NASH trials are also accurately examined. We conclude that the high heterogeneity of NASH, resulting from variable genetic backgrounds, exposure, and responses to different metabolic stresses, susceptibility to hepatocyte lipotoxicity, and differences in repair-response, calls for personalized medicine approaches involving research on noninvasive biomarkers. Future NASH trials should aim at achieving a complete assessment of systemic determinants, modifiers, and correlates of NASH, thus adopting a more holistic and unbiased approach, notably including cardiovascular–kidney–metabolic outcomes, without restricting therapeutic perspectives to histological surrogates of liver-related outcomes alone.

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Section: Pitfalls In Endpoints In Nash Clinical Trialsmentioning

confidence: 99%

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

Lonardo,

Ballestri,

Mantovani

et al. 2024

Metabolites

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“…A recent systematic review by Zeng et al analyzed lncRNA and circRNA patterns in MASLD. Differences were observed in the expression of twenty-two lncRNAs: fifteen of these were upregulated (e.g., NEAT1, lncARSR), while the other six were downregulated (e.g., lncSPARCL1) in patients with MASLD [ 101 ]. Similarly, in the study by Sun et al, substantial differences in lncRNA expression profiles between MASLD and normal control tissues were identified [ 102 ].…”

Section: Ev-enclosed Non-coding Rnas As Biomarkers For Detection and ...mentioning

confidence: 99%

“…Among these, NEAT1, MEG3, and MALAT1 showed great potential as biomarkers for the disease. Differentially expressed circRNAs were also observed in patients with MASLD and MASH (e.g., circRNA_0046367, circRNA_0001805, SCAR) [ 101 ]. However, hitherto, knowledge regarding the utility of lncRNAs and circRNAs encapsulated in EVs as biomarkers for MASH/MASLD is scarce.…”

Section: Ev-enclosed Non-coding Rnas As Biomarkers For Detection and ...mentioning

confidence: 99%

Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases

Ferro,

Saccu,

Mattivi

et al. 2024

Biomolecules

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In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies.

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“…Altered circRNA expression profiles have been associated with NAFLD and obesity, affecting the pathways involved in insulin resistance and lipid metabolism [ 123 ]. Lastly, several lncRNAs have been found to be dysregulated in NAFLD, potentially influencing the pathways related to inflammation, lipid metabolism, and fibrosis [ 118 ].…”

Section: Noncoding Rnasmentioning

confidence: 99%

Epigenetic Regulation in Lean Nonalcoholic Fatty Liver Disease

Αγγελετοπούλου

Kalafateli

Tsounis

et al. 2023

IJMS

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Nonalcoholic fatty liver disease (NAFLD), the most prominent cause of chronic liver disease worldwide, is a rapidly growing epidemic. It consists of a wide range of liver diseases, from steatosis to nonalcoholic steatohepatitis, and predisposes patients to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. NAFLD is strongly correlated with obesity; however, it has been extensively reported among lean/nonobese individuals in recent years. Although lean patients demonstrate a lower prevalence of diabetes mellitus, central obesity, dyslipidemia, hypertension, and metabolic syndrome, a percentage of these patients may develop steatohepatitis, advanced liver fibrosis, and cardiovascular disease, and have increased all-cause mortality. The pathophysiological mechanisms of lean NAFLD remain vague. Studies have reported that lean NAFLD demonstrates a close association with environmental factors, genetic predisposition, and epigenetic modifications. In this review, we aim to discuss and summarize the epigenetic mechanisms involved in lean NAFLD and to introduce the interaction between epigenetic patterns and genetic or non genetic factors. Several epigenetic mechanisms have been implicated in the regulation of lean NAFLD. These include DNA methylation, histone modifications, and noncoding-RNA-mediated gene regulation. Epigenetics is an area of special interest in the setting of lean NAFLD as it could provide new insights into the therapeutic options and noninvasive biomarkers that target this under-recognized and challenging disorder.

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LncRNA and circRNA in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review

Cited by 16 publications

References 67 publications

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases

Epigenetic Regulation in Lean Nonalcoholic Fatty Liver Disease

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