MicroRNA Biomarkers of Toxicity in Biological Matrices

Harrill, Alison H.; McCullough, Shaun D.; Wood, Charles E.; Kahle, Juliette J.; Chorley, Brian N.

doi:10.1093/toxsci/kfw184

Cited by 4 publications

(3 citation statements)

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“…miRNAs have been shown to be involved in various biological process including proliferation, differentiation, development, and development of diseases such as cancers and organ injuries (Li & Kowdley, 2012; Pavkovic & Vaidya, 2016; Peng & Croce, 2016; Yokoi & Nakajima, 2013). Extracellular miRNAs have received increasing attention in the past decade as biomarkers for cancers and organ injuries (Harrill et al, 2016; Sohel, 2020) because miRNAs are relatively stable for hours in the body fluid including plasma/serum, saliva, semen, and urine (Weber et al, 2010). This is because they are encapsulated in exosomes, microvesicles, and apoptotic bodies (Bayraktar et al, 2017) and are associated with RNA‐binding proteins, including high‐density lipoprotein (HDL) (Vickers et al, 2011), argonaute 2 (Arroyo et al, 2011), or nucleophosmin 1 (Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

Oda

Hirabuki

Takeuchi

et al. 2021

J of Applied Toxicology

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MicroRNAs (miRNA) have received considerable attention as potential biomarkers for drug‐induced liver injury. We recently reported that the plasma levels of miR‐143‐3p and miR‐218a‐5p increased in severe cholestasis in rats. This study aimed to investigate whether these miRNAs increase in a severity‐dependent manner and to elucidate their pathophysiological roles in cholestasis. Male Sprague–Dawley rats were orally administered different doses of α‐naphthylisothiocyanate or 4,4‐methylenedianiline to induce acute cholestasis. They were also orally administered acetaminophen or thioacetamide to induce hepatocellular injury. We found that plasma miR‐143‐3p and miR‐218a‐5p levels increased in a dose‐dependent manner in cholestatic rats but not in hepatocellular injury. Bioinformatic analysis provided putative target genes of hsa‐miR‐218‐5p, rno‐miR‐218a‐5p, and mmu‐miR‐218‐5p, among which GNAI2, PPP1CB, and PPP2R5A were experimentally validated as their direct target genes in human cholangiocyte line MMNK‐1. Proliferation of MMNK‐1 cells was significantly suppressed after overexpression of miR‐218‐5p and transduction of siRNAs for GNAI2, PPP1CB, and PPP2R5A. In the cholestatic livers of rats, Ppp1cb and Ppp2r5a expression levels decreased, whereas Gnai2 expression levels increased compared with those in vehicle‐treated rats, suggesting that Ppp1cb and Ppp2r5a may be under the control of miR‐218a‐5p in vivo. In conclusion, our data suggest that miR‐218(a)‐5p is involved in the suppression of cholangiocyte proliferation by inhibiting the expression of PPP1CB and PPP2R5A, thereby contributing to the pathogenesis of cholestasis; and miR‐218a‐5p leaks into the plasma probably from damaged cholangiocytes in a severity‐dependent manner in rats. Therefore, miR‐218a‐5p overexpression could be one of the underlying mechanisms of acute cholestatic liver injury in rats.

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Section: Introductionmentioning

confidence: 99%

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

Oda

Hirabuki

Takeuchi

et al. 2021

J of Applied Toxicology

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“…MicroRNAs (miRNAs) are short, non-coding RNAs of approximately 22 nucleotides in length that regulate gene expression by selectively binding to the 3ʹ untranslated regions of messenger RNAs (mRNAs), thereby inhibiting translation or degrading the transcript [1,2]. Recently there has been great enthusiasm for using miRNAs as biofluid-based biomarkers of diseases and toxicity [3][4][5][6][7][8][9]. miRNAs are highly sequence conserved across mammalian species and some are stable in extracellular environments upon release from cells, either by active transport or passively through membrane leakage [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

RATEmiRs: the rat atlas of tissue-specific and enriched miRNAs for discerning baseline expression exclusivity of candidate biomarkers

Bushel

Caiment

et al. 2020

RNA Biology

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MicroRNAs (miRNAs) are small RNAs that regulate mRNA expression and have been targeted as biomarkers of organ damage and disease. To explore the utility of miRNAs to assess injury to specific tissues, a tissue atlas of miRNA abundance was constructed. The Rat Atlas of Tissue-specific and Enriched miRNAs (RATEmiRs) catalogues miRNA sequencing data from 21 and 23 tissues in male and female Sprague-Dawley rats, respectively. RATEmiRs identifies tissue-enriched (TE), tissue-specific (TS), or organ-specific (OS) miRNAs via comparisons of one or more tissue or organ vs others. We provide a brief overview of RATEmiRs and present how to use it to detect miRNA expression abundance of candidate biomarkers as well as to compare the expression of miRNAs between rat and human. The database is

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“…Unlike the traditional solid tissue biopsies, the liquid biopsies are noninvasive or minimally invasive to subjects and patients [2,3]. Liquid biopsies offer great promise for rapid and cost-effective detection of toxicity or disease at an early stage when it is most reversable, curable or actionable [3][4][5][6][7][8]. For example, quantification of KIM-1 levels in urine have been qualified by the US Food and Drug Administration (FDA) to detect certain kidney injuries using liquid biopsies [9].…”

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confidence: 99%

Reproducibility Challenges for Biomarker Detection with Uncertain But Informative Experimental Data

et al. 2020

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Recent studies have revealed that circulating microRNAs are promising biomarkers for detecting toxicity or disease. Quantitative real-time polymerase chain reaction (qPCR) is often used to measure the levels of microRNAs. Besides complete and certain data, investigators inevitably have observed technically incomplete or uncertain qPCR data. Investigators usually set incomplete observations equal to the maximum quality number of qPCR cycles, apply the complete-observation method, or choose not to analyze targets with incomplete observations. Using biostatistical knowledge and published studies, we show that three commonly applied methods tend to cause biased inference and decrease reproducibility in biomarker detection. More efforts are needed to address the challenges to identify and detect reliable, novel circulating biomarkers in liquid biopsies.

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MicroRNA Biomarkers of Toxicity in Biological Matrices

Cited by 4 publications

References 0 publications

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

Plasma miR‐218a‐5p as a biomarker for acute cholestatic liver injury in rats and investigation of its pathophysiological roles

RATEmiRs: the rat atlas of tissue-specific and enriched miRNAs for discerning baseline expression exclusivity of candidate biomarkers

Reproducibility Challenges for Biomarker Detection with Uncertain But Informative Experimental Data

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