Comparison of microRNA expressions for the identification of chemical hazards in in vivo and in vitro hepatic injury models

Abstract

Biofluid‐based biomarkers provide an efficient tool for hazard identification of chemicals. Here, we explored the potential of microRNAs (miRNAs) as biomarkers for hepatotoxicity of chemicals by linking in vitro to in vivo animal models. A search of the literature identified candidate circulating miRNA biomarkers of chemical‐induced hepatotoxicity. The expression of candidate miRNAs (miR‐122, miR‐151a, miR‐192, miR‐193a, miR‐194, miR‐21, miR‐29c), was determined by real‐time reverse transcription‐polymerase chain reaction in in vivo acute liver injury induced by acetaminophen, and then were further compared with those of in vitro cell assays. Candidate miRNAs, except miR‐29c, were significantly or biologically upregulated by acetaminophen, at a dose that caused acute liver injury as confirmed by hepatocellular necrosis. Except miR‐122 and miR‐193a, other miRNAs elevated in in vivo models were confirmed by in vitro models using HepG2 cells, whereas they failed by in vitro models using human primary hepatocytes. These findings indicate that certain miRNAs may still have the potential of toxicological biomarkers in linking in vitro to in vivo hepatotoxicity.

MicroRNAs as Plasma Biomarkers of Hepatocellular Carcinoma in Patients with Liver Cirrhosis—A Cross-Sectional Study

“…In line with our results, Xue et al [46] found elevated miR-93 in the circulation of HCC patients, although not evaluated in combination with AFP and DCP. On the other hand, to the best of our knowledge, miR-151a has not been associated with HCC, but with toxic liver damage and obesity [47,48], and other diseases like atopic dermatitis [49] and glioblastoma [50].…”

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

“…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].…”

Reproducibility Challenges for Biomarker Detection with Uncertain But Informative Experimental Data

“…MicroRNAs can be released from cells into biofluids, including blood, urine, cerebrospinal fluid and saliva [20]. MicroRNAs are stable and readily detectable in biofluids, and numerous studies have reported that their levels in biofluids reflect changes at the tissue level of several organs, including liver, kidney, heart and brain [10,[21][22][23][24].…”