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

Torres, Jorge-Luis; Novo-Veleiro, Ignacio; Manzanedo, L; Alvela-Suárez, Lucía; Macías, Ronald; Laso, Francisco‐Javier; Marcos, Miguel

doi:10.3748/wjg.v24.i36.4104

Cited by 98 publications

(75 citation statements)

References 169 publications

(163 reference statements)

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“…In addition, a miR-34a inhibitor has been identified that may effectively protect against sevoflurane-induced hippocampal apoptosis by targeting Wnt1 and activating the Wnt/β-catenin pathway [34]. miR-34a is involved in the pathogenesis of non-alcoholic fatty liver disease [35] and is down-regulated in genetically improved farmed tilapia (Oreochromis niloticus) when they are fed a high-fat diet [36]. However, little is known about the role of miR-34a in porcine adipogenesis.…”

Section: Introductionmentioning

confidence: 99%

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Wang

Ding

et al. 2020

BMC Genet

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Background: Intramuscular fat (IMF) content is an important factor in porcine meat quality. Previously, we showed that miR-34a was less abundant in liver tissue from pigs with higher backfat thickness, compared to pigs with lower backfat thickness. The purpose of this present study was to explore the role of miR-34a in adipogenesis. Result: Bioinformatics analysis identified Acyl-CoA synthetase long chain family member 4 (ACSL4) as a putative target of miR-34a. Using a luciferase reporter assay, we verified that miR-34a binds the ACSL4 mRNA at the 3'UTR. To examine the role of the miR-34a-ACSL4 interaction in IMF deposition in the pig, mRNA and protein expression of the ACSL4 gene was measured in primary intramuscular preadipocytes transfected with miR-34a mimic and inhibitor. Our results showed that ACSL4 is expressed throughout the entire differentiation process in pig preadipocytes, similar to the lipogenesis-associated genes PPARγ and aP2. Transfection with miR-34a mimic reduced lipid droplet formation during adipogenesis, while miR-34a inhibitor increased lipid droplet accumulation. Transfection with miR-34a mimic also reduced the mRNA and protein expression of ACSL4 and lipogenesis genes, including PPARγ, aP2, and SREBP-1C, but increased the expression of steatolysis genes such as ATGL and Sirt1. In contrast, the miR-34a inhibitor had the opposite effect on gene expression. Further, knockdown of ACSL4 decreased lipid droplet accumulation. Conclusions: Our results support the hypothesis that miR-34a regulates intramuscular fat deposition in porcine adipocytes by targeting ACSL4.

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Section: Introductionmentioning

confidence: 99%

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Wang

Ding

et al. 2020

BMC Genet

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“…Similarly, a recent study reported that miRNA-34a had moderate accuracy for distinguishing between NASH and NAFL (AUROC=0.78) [44]. Our study involved a total of 14 miRNAs, which have several roles in the pathogenesis of NAFLD [14,45], such as, lipid synthesis (miRNA-122), fatty acid b-oxidation (miRNA-34a, -122), endoplasmic reticulum stress (miRNA-30, -34a, -122), in ammation (miRNA-34a, -99a, -146b), brosis (miRNA-122), tumorigenesis (miRNA-99a), and cell autophagy and apoptosis (miRNA-34a). The relationships between miRNAs and NASH pathogenesis can be both one-to-many and many-to-one.…”

Section: Discussionmentioning

confidence: 74%

Efficacy of serum miRNA test as a non-invasive method to diagnose nonalcoholic steatohepatitis: a systematic review and meta-analysis.

Xin

Zhan

Chen

et al. 2020

Preprint

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1. Background: Nonalcoholic steatohepatitis (NASH) is a key turning point during the progression of nonalcoholic fatty liver disease (NAFLD). Recent studies have shown that serum miRNA tests may be effective in the diagnosis of NAFLD. We conducted a meta-analysis to assess the evidence for the diagnostic efficacy of serum miRNAs in patients with NAFLD and its subtype, NASH, in particular. 2. Methods: After a systematic review, sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC) were pooled to determine the efficacy of serum miRNA test for the diagnosis of NAFLD and NASH. Clinical utility was evaluated by Fagan’s nomogram and likelihood ratio scattergram. Heterogeneity was evaluated by subgroup analysis and meta-regression. Publication bias was detected by Deeks’ funnel plot. 3. Results: We included 27 trials containing 1775 NAFLD patients (including simple steatosis and NASH) and 586 NASH patients. For NAFLD vs NASH, the pooled sensitivity, specificity, and AUROC were (0.71 vs. 0.74), (0.76 vs. 0.85) and (0.80 vs. 0.86), respectively. Serum miRNA had high accuracy for distinguishing NASH from simple steatosis, with an AUROC of 0.91. Among the most commonly studied serum miRNAs , miRNA-34a showed moderate diagnostic accuracy for NAFLD and the lowest heterogeneity (sensitivity I 2 = 5.73%, specificity I 2 = 33.16%, AUROC = 0.85). According to subgroup analysis and meta-regression, a lower BMI ( < 30 kg/m 2 ) might be a crucial source of heterogeneity. 4.Conclusions: As a novel non-invasive method, serum miRNA test exhibited robust diagnostic efficacy for NASH. Among these well-studied miRNAs, miRNA-34a was more available for diagnosis. Diagnosis of NAFLD by serum miRNA is more likely to be accurate in patients with BMI ≥ 30kg/m 2 .

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“…Notably, in our study, a high accuracy of serum miRNA in discriminating NASH from NAFL was found with AUROC at 0.91. Similarly, a recent study reported that miRNA-34 had moderate accuracy to distinguish between NAFL and NASH [44]; (2) Our study involved a total of 14 miRNAs, which played roles in multiple pathological processes of NAFLD [14,45]. For example, lipid synthesis (miRNA-122), fatty acid b-oxidation (miRNA-122, -34a), endoplasmic reticulum stress (miRNA-122, -34a, -30), inflammation (miRNA-146b, -99a), fibrosis (miRNA-122), tumorigenesis (miRNA-99a), cell autophagy and apoptosis (miRNA-34a).…”

Section: Discussionmentioning

confidence: 77%

“…Due to limited researches, we did not compare the differences between miRNA-34a in the diagnosis of NAFLD and NASH. As a valuable reference, a study has shown that miRNA-34a can distinguish NASH from NAFL [45] Fourthly, the performance of serum miRNA in the diagnosis of NAFLD may depends on BMI. In our subgroup analysis, miRNA showed more accurate efficacy in this NAFLD cases with BMI ≥ 30 kg/m 2 .…”

Section: Discussionmentioning

confidence: 99%

Diagnostic efficacy of serum miRNA as a non-invasive method for nonalcoholic steatohepatitis: a systematic review and meta-analysis.

Xin

Zhan

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

1. Background: Nonalcoholic steatohepatitis (NASH) is a key turning point in the progression of nonalcoholic fatty liver disease (NAFLD). As a non-invasive method , serum miRNA levels may provide an effective reference for the diagnosis of NASH. This article systematically reviewed related diagnostic trials to compare the difference in the efficacy of serum miRNAs in the diagnosis of NAFLD and its subtype, NASH, and identify the influencing factors. 2. Methods: We pooled the sensitivity (SEN), specificity (SPE), and area under receiver operating characteristics (AUROC) of each trail to determine the efficacy of serum miRNAs in the diagnosis of NAFLD and NASH; Clinical utility was evaluated by Fagan`s nomogram; Heterogeneity was evaluated by subgroup analysis and meta-regression. Publication bias was detected by Deek’s funnel plot. 3. Results: We included 9 articles consisting of 27 trials and 2361 cases, 1775 NAFLD patients (not distinguishing between simple steatosis and NASH) and 586 NASH patients were collected. All cases were confirmed by biopsy. For NAFLD and NASH, the pooled values were SEN (0.71 vs. 0.74), SPE (0.76 vs. 0.85) and AUROC (0.80 vs. 0.86). miRNA had a high accuracy in distinction NASH from simple steatosis with AUROC at 0.91. Among the well-studied serum miRNAs, miRNA-34a showed a moderate accuracy with the lowest heterogeneity in diagnosing NAFLD (SPE I 2 : 5.73%, SPE I 2 : 33.16%, AUROC: 0.85). According to subgroup analysis and meta-regression, lower BMI ( <30kg/m 2 ) may be a crucial source of heterogeneity and reduced the performance of serum miRNA in the diagnosis of NAFLD. 4. Conclusions: As a non-invasive method, serum miRNA should be considered a promising parameter in the diagnosis of NASH. Generally, NAFLD patients with higher BMI ( ≥ 30kg/m 2 ) are more likely to be diagnosed accurately by serum miRNA.

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

Cited by 98 publications

References 169 publications

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Efficacy of serum miRNA test as a non-invasive method to diagnose nonalcoholic steatohepatitis: a systematic review and meta-analysis.

Diagnostic efficacy of serum miRNA as a non-invasive method for nonalcoholic steatohepatitis: a systematic review and meta-analysis.

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