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Identification of translational microRNA biomarker candidates for ketoconazole-induced liver injury using next-generation sequencing

ABSTRACT: Identification of translational microRNA biomarker candidates for ketoconazole-induced liver injury using next-generation sequencing

PROVIDER: PRJNA667935 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12789662.fastq.gz	Fastqsanger.gz
	SRR12789663.fastq.gz	Fastqsanger.gz
	SRR12789664.fastq.gz	Fastqsanger.gz
	SRR12789665.fastq.gz	Fastqsanger.gz
	SRR12789666.fastq.gz	Fastqsanger.gz

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Identification of translational microRNA biomarker candidates for ketoconazole-induced liver injury using next-generation sequencing

Project description:Drug induced liver injury (DILI) is a leading cause of acute liver failure. Reliable and translational biomarkers are needed for early detection of DILI. microRNAs (miRNAs) have received wide attention as a novel class of potential DILI biomarkers. However, it is unclear how DILI drugs other than acetaminophen may influence miRNA expression or which miRNAs could serve as useful biomarkers in humans. We selected ketoconazole (KCZ), a classic hepatotoxin, to study miRNA biomarkers for DILI as a proof-of-concept for a workflow that integrated in vivo, in vitro, and bioinformatics analyses. We examined hepatic miRNA expression in KCZ-treated rats at multiple doses and durations using miRNA-sequencing and correlated our results with conventional DILI biomarkers such as liver histology. Significant dysregulation of rno-miR-34a-5p, rno-miR-331-3p, rno-miR-15b-3p, and rno-miR-676 was associated with cytoplasmic vacuolization, a phenotype in rat livers with KCZ-induced injury, which preceded the elevation of serum liver transaminases (ALT and AST). Between rats and humans, miR-34a-5p, miR-331-3p, and miR-15b-3p were evolutionarily conserved with identical sequences, whereas miR-676 showed 73% sequence similarity. Using quantitative PCR, we found that the levels of hsa-miR-34a-5p, hsa-miR-331-3p, and hsa-miR-15b-3p were significantly elevated in the culture media of HepaRG cells treated with 100 mM KCZ (a concentration that could induce cytotoxicity). Additionally, we computationally characterized the miRNA candidates for their gene targeting, target functions, and miRNA/target evolutionary conservation. In conclusion, we identified miR-34a-5p, miR-331-3p, and miR-15b-3p as translational biomarker candidates for early detection of KCZ-induced liver injury with a workflow applicable to computational toxicology studies.

2020-10-23 | GSE159200 | GEO

Identification of Translational microRNA Biomarker Candidates for Ketoconazole-Induced Liver Injury Using Next-Generation Sequencing.

Project description:Drug-induced liver injury (DILI) is a leading cause of acute liver failure. Reliable and translational biomarkers are needed for early detection of DILI. microRNAs (miRNAs) have received wide attention as a novel class of potential DILI biomarkers. However, it is unclear how DILI drugs other than acetaminophen may influence miRNA expression or which miRNAs could serve as useful biomarkers in humans. We selected ketoconazole (KCZ), a classic hepatotoxin, to study miRNA biomarkers for DILI as a proof of concept for a workflow that integrated in vivo, in vitro, and bioinformatics analyses. We examined hepatic miRNA expression in KCZ-treated rats at multiple doses and durations using miRNA-sequencing and correlated our results with conventional DILI biomarkers such as liver histology. Significant dysregulation of rno-miR-34a-5p, rno-miR-331-3p, rno-miR-15b-3p, and rno-miR-676 was associated with cytoplasmic vacuolization, a phenotype in rat livers with KCZ-induced injury, which preceded the elevation of serum liver transaminases (ALT and AST). Between rats and humans, miR-34a-5p, miR-331-3p, and miR-15b-3p were evolutionarily conserved with identical sequences, whereas miR-676 showed 73% sequence similarity. Using quantitative PCR, we found that the levels of hsa-miR-34a-5p, hsa-miR-331-3p, and hsa-miR-15b-3p were significantly elevated in the culture media of HepaRG cells treated with 100 µM KCZ (a concentration that induced cytotoxicity). Additionally, we computationally characterized the miRNA candidates for their gene targeting, target functions, and miRNA/target evolutionary conservation. In conclusion, we identified miR-34a-5p, miR-331-3p, and miR-15b-3p as translational biomarker candidates for early detection of KCZ-induced liver injury with a workflow applicable to computational toxicology studies.

| S-EPMC7855383 | biostudies-literature

Identification of translational microRNA biomarker candidates for nano-polystyrene induced brain injury using next-generation sequencing

Project description:Identification of translational microRNA biomarker candidates for nano-polystyrene induced brain injury using next-generation sequencing

| PRJNA670714 | ENA

Identification of translational ncRNA biomarker candidates for nano-polystyrene induced brain injury using next-generation sequencing

Project description:Identification of translational ncRNA biomarker candidates for nano-polystyrene induced brain injury using next-generation sequencing

| PRJNA671603 | ENA

miRNA profiling of putative biomarker candidates in Mycobacterium avium subsp. paratuberculosis-infected cattle

Project description:Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease that is a chronic wasting disease in ruminants. Spread of MAP is mainly provoked by a long subclinical stage during which MAP is shed into the environment with feces; accordingly, detection of subclinical animals is very important to its control. Therefore, the current diagnostic methods are not suitable for detection of subclinical animals. In this study, we conducted to develop a diagnostic method for analysis of the expression of genes of prognostic potential biomarker candidates in cattle naturally infected with MAP. We conducted miRNA-Seq to evaluate potential biomarker candidates. Experimental animals were divided into four groups based on fecal MAP PCR, serum ELISA, and clinical sign.

2021-02-05 | GSE166230 | GEO

Identification of translational microRNA biomarker candidates for nano-polystyrene induced brain injury using next-generation sequencing

Project description:The exposure to nano-plastics affects mammalian neurotoxic hazard characterization remains to be determined. Our aim was to investigate the neurotoxicity of nano-plastics in rodents. Animals were randomly divided into two groups: a control group and 50 mg/kg body weight PS NPs treatment groups. Before treatment, animals were fasted overnight. PS NPs were suspended into waters, vigorously stirred. The PS NPs via oral gavage once per day and for 6 months. The mice were treated with water in control group. We found that exposure to PS NPs caused cognitive decline. PS NPs exposure influenced the prefrontal cortex cells with more pathological alteration with increasing dosage. High-throughput RNA sequencing was conducted to explore miRNA expression in prefrontal cortex. Twenty-nine differentially expressed miRNAs were detected, including 12 upregulated and 17 downregulated miRNAs. This finding provided a reference for further studies on the development mechanisms of ncRNA during cognitive dysfunction.

2023-10-01 | GSE159881 | GEO

Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation

Project description:Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation

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Genomic analysis of ketoconazole resistance in the dandruff-associated cutaneous yeast Malassezia restricta.

Project description:To understand ketoconazole resistance mechanism in M. restricta, we investigated differentially expressed genes in the azole resistant isolates using transcriptome profile. Transcriptomes of ketoconazole susceptible and resistant M. restricta cells in the absence and precence of ketoconazole were compared and analyzed by RNA sequencing.

2020-12-05 | GSE141548 | GEO

The genomic tandem quadruplication is associated with ketoconazole resistance of Malassezia pachydermatis

Project description:Purpose: Understanding the ketoconazole resistance mechanism in Malassezia pachydermatis Methods: The transcriptome profile of the ketoconazole resistant M. pachydermatis KCTC 27587 cells compared to that of ketoconazole sensitive M. pachydermatis CBS 1879 cells were generated by RNA-Seq using Illumina HiSeq. Results: The expressions of genes in the region of quadruplicated chromosome 4 were up-regulated.

2019-02-07 | GSE118354 | GEO

Transcriptional profile of Candida albicans DAY286 culture without ketoconazole versus DAY286 culture with 0.04 Î¼g/ml ketoconazole, both at 20% oxygen (normoxia).

Project description:Whole genome microarray were used to generate the transcriptional profile of C.albicans in the presence of ketoconazole. RNA was isolated from DAY286 grown with or without ketoconazole in YPD medium in normoxia at 30 degree Celsius for 3.5 h, and labeled with Cy3 or Cy5. Four independent biological replicates were compared. 2 dye swaps were perfomed so that 2 out of 4 samples isolated from DAY286 in normoxic culture without ketoconazole were labeled with Cy3, and 2 were labeled with Cy5.

2010-11-15 | E-GEOD-24074 | biostudies-arrayexpress

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