title: Arsenic exposure triggers a shift in microRNA expression.
abstract: Exposure to inorganic Arsenic (iAs) through drinking water is a major public health problem affecting most countries. iAs has been classified by the International Agency for Research on Cancer as Group 1: "Carcinogenic to humans". Although numerous studies have shown the related adverse effects of iAs, sensitive appropriate biomarkers for studies of environmental epidemiology are still required. The present work aims at investigate the role of microRNAs (miRNAs), powerful negative regulators of gene expression, playing a key role in many physiological and pathological cellular processes, in iAs exposure. To this end, we analyzed miRNA changes in expression profile triggered by iAs exposure in Jurkat cell line. We used microarray technology to profile the expression of miRNAs following 2 μmol/L sodium arsenite treatment at different time points. Moreover, we performed phenotypic analysis of iAs treated cells. Real Time Polymerase Chain Reaction (RT-PCR) was used to validate miRNA microarray data and to assay expression modulation of selected relevant mRNAs. Finally, bioinformatics techniques were applied to reconstruct iAs-relevant molecular pathways and miRNA regulatory networks from the expression data. We report miRNAs modulated after iAs treatment in Jurkat cells. In particular, we highlight 36 miRNAs exhibiting consistent dysregulation and particularly a panel of 8 miRNAs which we also validated by RT-PCR analysis. Computational analysis of lists of putative target genes for these 8 miRNAs points to an involvement in arsenic-response pathways, for a subset of them, that were analyzed by RT-PCR. Furthermore, iAs exposure reveals induction of cell cycle progression and the failure of apoptosis, supporting the idea of iAs carcinogenic activity. Our study provides a list of miRNAs whose expression levels are affected by iAs treatment, corroborating the importance of proceeding with the hunt for specific subset of miRNAs, which can serve as potential biomarkers of iAs effects with useful diagnostic value.
authors: Italian Workers' Compensation Authority (INAIL), Department of Production Plants and Anthropic Settlements (DIPIA) Via Alessandria, 220/E, 00198 Rome, Italy. Electronic address: e.sturchio@inail.it.
authors: Elena
authors: E
authors: Sturchio
authors: University of Rome "La Sapienza"-BCE, Viale del Policlinico 155, 00161, Rome, Italy.
authors: Teresa
authors: T
authors: Colombo
authors: Italian Workers' Compensation Authority (INAIL), Department of Production Plants and Anthropic Settlements (DIPIA) Via Alessandria, 220/E, 00198 Rome, Italy.
authors: Priscilla
authors: P
authors: Boccia
authors: University of Rome "La Sapienza"-BCE, Viale del Policlinico 155, 00161, Rome, Italy.
authors: Nicoletta
authors: N
authors: Carucci
authors: Italian Workers' Compensation Authority (INAIL), Department of Production Plants and Anthropic Settlements (DIPIA) Via Alessandria, 220/E, 00198 Rome, Italy.
authors: Claudia
authors: C
authors: Meconi
authors: Laboratory for Environmental and Toxicological Measurements, IRCCS Pavia, S. Maugeri Foundation, Via S. Maugeri, 8, 27100, Pavia, Italy.
authors: Claudio
authors: C
authors: Minoia
authors: University of Rome "La Sapienza"-BCE, Viale del Policlinico 155, 00161, Rome, Italy.
authors: Giuseppe
authors: G
authors: Macino
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D015415:Biomarkers / Q000737:chemistry; D004784:Environmental Monitoring / Q000379:methods; D015870:Gene Expression; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D015415:Biomarkers; C000715470:MAS1 protein, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: AP-1; BACH1; BTB and CNC homology 1, basic leucine zipper transcription factor 1; Biomarkers; CDK; CYP1A1; ERK; FACS; Fluorescence Activated Cell Sorting; HMOX; Inorganic arsenic; JNK; JUNB; Jun B proto-oncogene; MAP; NF-kB; NRF-1; Networks; Predicted target genes; RNF4; ROS; RT-PCR; Reactive Oxygen Species; Real Time Polymerase Chain Reaction; Ring Finger Protein 4; SP1; SUMO; Small Ubiquitin-like Modifier; TGFβ1; Transforming Growth Factor Beta 1; activator protein-1; c-Jun N-terminal kinase; cyclin-dependent kinase; cytochrome P450, family 1, subfamily A, polypeptide 1; extracellular signal-regulated kinase; heme oxygenase 1; iAS; inorganic Arsenic; miRNA; microRNA; microRNA expression profile; microRNA regulatory; mitogen-activated protein; nuclear factor-kB; nuclear respiratory factor-1; transcription factor Sp1