Association of Circulating Serum miR-34a and miR-122 with Dyslipidemia among Patients with Non-Alcoholic Fatty Liver Disease

Salvoza, Noel; Klinzing, David C.; Gopez-Cervantes, Juliet; Baclig, Michael O

doi:10.1371/journal.pone.0153497

Cited by 124 publications

(138 citation statements)

References 38 publications

(44 reference statements)

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…We also found miR‐34a‐5p and miR‐365a‐3p to be up‐regulated in serum of CFLD compared to CFnoLD children. Increased serum levels of miR‐34a have been reported in CLDs such as hepatitis C and NAFLD . miR‐34a has been associated with liver regeneration, having a direct repressor effect on hepatocyte proliferation and senescence in alcoholic liver injury and in animal models of partial hepatectomy .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

et al. 2018

View full text Add to dashboard Cite

Cystic fibrosis (CF)-associated liver disease (CFLD) is a hepatobiliary complication of CF. Current diagnostic modalities rely on nonspecific assessments, whereas liver biopsy is the gold standard to assess severity of fibrosis. MicroRNAs (miRNAs) regulate liver disease pathogenesis and are proposed as diagnostic biomarkers. We investigated the combined use of serum miRNAs and aspartate aminotransferase (AST) to platelet ratio (APRI) to diagnose and assess CFLD severity. This was a cross-sectional cohort study of the circulatory miRNA signature of 124 children grouped by clinical, biochemical, and imaging assessments as follows: CFLD (n = 44), CF patients with no evidence of liver disease (CFnoLD; n = 40), and healthy controls (n = 40). Serum miRNAs were analyzed using miRNA sequencing (miRNA-Seq). Selected differentially expressed serum miRNA candidates were further validated by qRT-PCR and statistical analysis performed to evaluate utility to predict CFLD and fibrosis severity validated by liver biopsy, alone or in combination with APRI. Serum miR-122-5p, miR-365a-3p, and miR-34a-5p levels were elevated in CFLD compared to CFnoLD, whereas miR-142-3p and let-7g-5p were down-regulated in CFLD compared to CFnoLD. Logistic regression analysis combining miR-365a-3p, miR-142-3p, and let-7g-5p with APRI showed 21 times greater odds of accurately predicting liver disease in CF with an area under the receiver operating characteristics curve (AUROC) = 0.91 (sensitivity = 83%, specificity = 92%; P < 0.0001). Expression levels of serum miR-18a-5p were correlated with increasing hepatic fibrosis (HF) stage in CFLD (r = 0.56; P < 0.0001), showing good diagnostic accuracy for distinguishing severe (F3-F4) from mild/moderate fibrosis (F0-F2). A unit increase of miR-18a-5p showed a 7-fold increased odds of having severe fibrosis with an AUROC = 0.82 (sensitivity = 93%, specificity = 73%; P = 0.004), indicating its potential to predict fibrosis severity. Conclusion: We identified a distinct circulatory miRNA profile in pediatric CFLD with potential to accurately discriminate liver disease and fibrosis severity in children with CF.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Interestingly, elevated miR-122 and miR-34a (another RYGB-downregulated miRNA in this study) have been associated with dyslipidemia in patients with non-alcoholic fatty liver disease. 33 In addition, miR-34a was reported as the most highly expressed hepatic miRNA in obese mice, where it impaired physiological postprandial responses through attenuation of FGF19 by directly targeting β-Klotho. 34 Our study demonstrated significant correlations between the change in circulating levels of miR-122 and miR-34a and the change in S G (Figures 3b and c), and between the changes in miR-34a and AIRg (Figure 3d).…”

Section: Discussionmentioning

confidence: 99%

Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk

et al. 2017

View full text Add to dashboard Cite

BACKGROUND/OBJECTIVES Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (SI) and β-cell function in obese non-diabetic subjects. Exercise also improves SI and may be an effective adjunct therapy to RYGB surgery. However, the mechanisms by which exercise or weight loss improve peripheral SI after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs) mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in SI and cardiometabolic risk factors. SUBJECTS/METHODS Ninety-four miRNAs implicated in metabolism were profiled in plasma samples from 22 severely obese subjects who were recruited 1–3 months after RYGB surgery and followed for 6 months of RYGB surgery-induced weight loss, with (exercise program (EX), N = 11) or without (CON, N = 11) an exercise training intervention. The subjects were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis. RESULTS Mirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, SI, and other cardiometabolic risk factors. CONCLUSIONS These findings present novel insights into the RYGB surgery-induced molecular changes and the effects of mild exercise to facilitate and/or maintain the benefits of a ‘comprehensive’ weight-loss intervention with concomitant improvements in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.

show abstract

“…It has also been proposed that liver cells release exosomes, containing miRNAs, as a defense mechanism [29,30,31]. Various studies have shown that miR-122 is released after chronic and acute liver damage [32,33,34]. However, due to different stimulants, miR-122 is released under different formations.…”

Section: Exosome-mediated Regulatory Effects In Livermentioning

confidence: 99%

Exosomes as miRNA Carriers: Formation–Function–Future

Odenthal

Fries

2016

IJMS

333

208

View full text Add to dashboard Cite

Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs). miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes’ formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine.

show abstract

Association of Circulating Serum miR-34a and miR-122 with Dyslipidemia among Patients with Non-Alcoholic Fatty Liver Disease

Cited by 124 publications

References 38 publications

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk

Exosomes as miRNA Carriers: Formation–Function–Future

Contact Info

Product

Resources

About