Evaluation of miR-122 to Predict High Dose Acetaminophen-Induced Liver Injury in Mice: The Combination Uses of 5-Fluorouracil

Munakata, Chie; Fuchigami, Yuki; Hiroishi, Shu; Haraguchi, Ayana; Hagimori, Masayori; Enomoto, Hatsune; Tachiki, Hidehisa; Kodama, Yukinobu; Sasaki, Hidetada; Kawakami, Shigeru

doi:10.1248/bpb.b18-00504

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…We searched the miRNA target gene prediction website database (http://www.targetscan.org) and found that TGFBRAP1 and miR-122 had potential binding sites ( Figure). MiR-122, which accounts for approximately 70% of the total miRNA in the adult liver, is involved in cell cycle progression, hepatocellular carcinogenesis, lipid metabolism, and fibrosis [20], so it was considered to have a high specificity in drug-induced liver injury with modest positive diagnostic effects [20, 21]. MiR-122 might inhibit hepatocellular carcinoma progression by downregulating TGFBRAP1 in the presence of the hepatitis C virus core, suggesting that the TGF- β /smad signalling pathway may be related to the expression level of miR-122, which plays an important role in drug-induced liver injury [22–24].…”

Section: Discussionmentioning

confidence: 99%

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury

Zhang

Zhao

Bai

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background. TGFBRAP1 and TGFBR2 play important roles in the TGF-β/smad signalling pathway and may disturb liver homeostasis by regulating liver injury and renewal. However, little is known about the association between their genetic polymorphisms and antituberculosis drug-induced liver injury (ATDILI), so we explored the association between their variants and the susceptibility to ATDILI. Materials and Methods. A total of 746 tuberculosis patients were prospectively enrolled, and fifteen selected SNPs were genotyped. The allele, genotype, and genetic model frequencies of the variants were compared between patients with or without ATDILI, as well as the joint effect analysis of SNP-SNP interactions. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated. Results. The A variant at rs17687727 was significantly associated with an increased risk for ATDILI (OR 1.55; 95% CI: 1.08–2.22; p=0.016), which is consistent with the results in the additive and dominant models. Other allele, genotype, and genetic model frequencies were similar in the two groups for the other fourteen SNPs (all p>0.05). Conclusion. Our study first implied that the A variant of rs17687727 in TGFBRAP1 influenced the susceptibility to ATDILI in first-line antituberculosis combination treatment in the Han Chinese population in a dependent manner.

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Section: Discussionmentioning

confidence: 99%

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury

Zhang

Zhao

Bai

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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“…Given their role as significantly important regulators of gene expression, microRNA (miRNA) molecules have emerged as reliable and potential biomarkers for the analysis of tumor progression and metastasis, disease-specific cells, , drug-triggered inflammation, , and radiation injury. , Previous reports have shown that radiotherapy is responsible for the so-called radiation-induced bystander effects during the comprehensive treatment of tumors and cancerous organs. , As a result, the ionizing radiation may cause damages to the adjacent normal tissues, which results in maligning consequences such as organ failure and internal bleeding. For example, it has been reported that the change in miRNA levels as a result of radiotherapy induces rectal damage in mice, which further results in cell apoptosis and DNA strand breaking .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Highly Sensitive Detection of Elevated Exosomal miR-122 Levels in Radiation Injury and Hepatic Inflammation Using an Aptamer-Functionalized SERS-Sandwich Assay

Muhammad

Shao

Liu

et al. 2021

ACS Appl. Bio Mater.

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Radiation-induced organ injury is one of the major fallouts noticed during radiotherapy treatment of malignancies and other detrimental radiation exposures. MicroRNA (miRNA), which is involved in multiple critical cellular processes, is released from the cells of damaged organs in cellular vesicles, commonly known as exosomes. Specifically, exosomal miR-122 is reported to be actively involved in radiation-actuated rectal and hepatic injuries or inflammation. In this work, we developed a surface-enhanced Raman spectroscopy (SERS) assay for the quantitative and targeted detection of exosomal miR-122 in mice after drug/radiation treatments. In particular, an aptamer-functionalized magnetic capturing element and Au shell nanoparticle (NP)-based SERS tags were utilized, which upon recognition of the target miRNA constituted a “sandwich” formation, with which an 8 fM limit of detection (LOD) could be achieved. Using this SERS assay, we further found that radiation injury led to the elevated expression of exosomal miR-122 in mice at 4 h postirradiation, confirmed by the quantitative real-time PCR method. It was demonstrated that the drug-induced hepatic inflammation could also be assessed via detecting miR-122 using this SERS method. As such, this work has demonstrated the achievement of a highly selective and sensitive probe of exosomal miRNA, which may thus open a gateway for promising usage in drug/radiation-induced inflammation.

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“…Human studies have largely focused on liver-associated miRNAs, specifically miR-122, which has repeatedly been found to be elevated in acetaminophen hepatotoxicity [21,22]. More recent studies have focused on expanded panels of miRNAs as markers, facilitators, and inhibitors of acetaminophen-induced hepatotoxicity [17,23].…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNA Profiles in Acetaminophen Toxicity

et al. 2019

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Introduction Acetaminophen toxicity has been associated with elevation of microRNAs. The present study was to evaluate overall microRNA profiles and previously identified microRNAs to differentiate acetaminophen (APAP) toxicity from other causes of transaminase elevation. Methods This was an observational study of adults with presumed acetaminophen toxicity at presentation. Serum samples were collected every 12 hours during hospitalization. Total miRNAs were extracted from plasma and levels of 327 microRNAs were quantified using real-time polymerase chain reaction. A standard measure of miRNA expression (delta-delta cycle threshold) was calculated for each microRNAs. A two-level cluster analysis was performed using a random k-means algorithm. Demographic and clinical characteristics of each cluster were compared using ANOVA, Wilcoxon rank sum, Kruskal-Wallis, and chi-square tests. Performance of specific miRNAs of interest was also evaluated. Results Twenty-seven subjects were enrolled (21 with a final diagnosis of acetaminophen toxicity), and a total of 61 samples were analyzed. Five clusters were identified, two of which demonstrated clear clinical patterns and included specific elevated miRNAs previously reported to be elevated in APAP toxicity patients. Features associated with clusters 1 and 5 included confirmed acetaminophen toxicity, high peak alanine aminotransferase, and late presentation. Clusters 2-4 contained lower peak microRNAs, lower peak alanine aminotransferase, and heterogeneous clinical characteristics. Conclusions Severe cases of acetaminophen toxicity showed two distinct patterns of microRNA elevation which were similar to previous work, while less severe cases were difficult to distinguish from non-acetaminophen-associated cases. Further work is needed to incorporate microRNA profiles into the diagnostic algorithm of acetaminophen toxicity.

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Evaluation of miR-122 to Predict High Dose Acetaminophen-Induced Liver Injury in Mice: The Combination Uses of 5-Fluorouracil

Cited by 8 publications

References 15 publications

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury

Highly Sensitive Detection of Elevated Exosomal miR-122 Levels in Radiation Injury and Hepatic Inflammation Using an Aptamer-Functionalized SERS-Sandwich Assay

Circulating microRNA Profiles in Acetaminophen Toxicity

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