Profiling Non-Coding RNA Changes Associated with 16 Different Engineered Nanomaterials in a Mouse Airway Exposure Model

Abstract

Perturbations in cellular molecular events and their associated biological processes provide opportunities for hazard assessment based on toxicogenomic profiling. Long non-coding RNAs (lncRNAs) are transcribed from DNA but are typically not translated into full-length proteins. Via epigenetic regulation, they play important roles in organismal response to environmental stress. The effects of nanoparticles on this important part of the epigenome are understudied. In this study, we investigated changes in lncRNA associated with hazardous inhalatory exposure of mice to 16 engineered nanomaterials (ENM)–4 ENM (copper oxide, multi-walled carbon nanotubes, spherical titanium dioxide, and rod-like titanium dioxide particles) with 4 different surface chemistries (pristine, COOH, NH2, and PEG). Mice were exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by cytological analyses and transcriptomic characterization of whole lung tissues. The number of significantly altered non-coding RNA transcripts, suggestive of their degrees of toxicity, was different for each ENM type. Particle surface chemistry and shape also had varying effects on lncRNA expression. NH2 and PEG caused the strongest and weakest responses, respectively. Via correlational analyses to mRNA expression from the same samples, we could deduce that significantly altered lncRNAs are potential regulators of genes involved in mitotic cell division and DNA damage response. This study sheds more light on epigenetic mechanisms of ENM toxicity and also emphasizes the importance of the lncRNA superfamily as toxicogenomic markers of adverse ENM exposure.

Identification of Candidate lncRNA and Pseudogene Biomarkers Associated with Carbon-Nanotube-Induced Malignant Transformation of Lung Cells and Prediction of Potential Preventive Drugs

“…In recent decades, mounting evidence has supported the idea that environmental pollutants (such as PM2.5 [ 33 , 34 , 35 ], nickel [ 36 ] and cadmium [ 37 , 38 ]) promote the malignant transformation of lung epithelial cells by changing the expression levels of ncRNAs. Dysregulation of ncRNA expression levels was also revealed to be a novel paradigm for interpretation of the toxicology of various nanoparticles [ 39 , 40 , 41 ]. However, to date, there has been no study exploring the molecular mechanisms associated with CNT-induced lung carcinogenesis from the perspective of lncRNAs and pseudogenes.…”

“…LncRNAs and pseudogenes were shown to be involved in various cell processes by regulating the expression levels of mRNAs via ceRNA [ 34 , 35 ] or co-expression [ 36 , 37 , 39 , 47 ] mechanisms. Thus, in our study, we constructed ceRNA and co-expression networks to identify the interaction pairs of hub lncRNAs and pseudogenes.…”

Where Is Nano Today and Where Is It Headed? A Review of Nanomedicine and the Dilemma of Nanotoxicology

“…The toxicogenomic profile was related to the shared expression of 242 long noncoding RNAs (lncRNAs) (Figure C). These 242 lncRNAs were upregulated relative to control and were highly associated with genes involved in cell cycle regulation, chromosomal organization, and DNA damage response, which may explain the relative cytotoxicity of the studied ENM . The exposure to an array of 28 ENMs also corroborated a dependence on gene toxicity, as 50 shared genes were associated with common adverse side effects observed for different ENMs in the study.…”

“…Toxicity is based on the expression of lncRNAs involved in regulating the DNA damage and repair response (d and e). Adapted with permission under a Creative Commons CC BY 4.0 License from ref . Copyright 2021, published by MDPI.…”

Recent Advancements in the Nanomaterial Application in Concrete and Its Ecological Impact

“…Consequences of nanomaterial exposure are not adequately realized, thus demanding studies to understand the interactions between nanomaterials and organic materials. Research works on the intake of many standard nanomaterials by mice generated understandings of the possible adversarial influences of nanomaterial exposure; however, generalization of the results was restricted by the experiment's subjects [170][171][172]. During recent years, toxicological examinations have been carried out with various kinds of engineered nanomaterials to understand their impact on the human body.…”