title: Formaldehyde-associated changes in microRNAs: tissue and temporal specificity in the rat nose, white blood cells, and bone marrow.
abstract: MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding their changes resulting from environmental exposures as they influence cellular signaling across various tissues. We set out to investigate miRNA responses to formaldehyde, a critical air pollutant and known carcinogen that disrupts miRNA expression profiles. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde for 7, 28, or 28 days followed by a 7-day recovery. Genome-wide miRNA expression profiles were assessed within the nasal respiratory epithelium, circulating white blood cells (WBC), and bone marrow (BM). miRNAs showed altered expression in the nose and WBC but not in the BM. Notably in the nose, miR-10b and members of the let-7 family, known nasopharyngeal carcinoma players, showed decreased expression. To integrate miRNA responses with transcriptional changes, genome-wide messenger RNA profiles were assessed in the nose and WBC. Although formaldehyde-induced changes in miRNA and transcript expression were largely tissue specific, pathway analyses revealed an enrichment of immune system/inflammation signaling in the nose and WBC. Specific to the nose was enrichment for apoptosis/proliferation signaling, involving let-7a, let-7c, and let-7f. Across all tissues and time points assessed, miRNAs were predicted to regulate between 7% and 35% of the transcriptional responses and were suggested to play a role in signaling processes including immune/inflammation-related pathways. These data inform our current hypothesis that formaldehyde-induced inflammatory signals originating in the nose may drive WBC effects.
authors.affiliation: * Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, North Carolina 27599;
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rager
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Moeller
authors.forename: Sloane K
authors.initials: SK
authors.lastname: Miller
authors.forename: Dean
authors.initials: D
authors.lastname: Kracko
authors.forename: Melanie
authors.initials: M
authors.lastname: Doyle-Eisele
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity*; D055106:Genome-Wide Association Study; D019570:Inhalation Exposure; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000393:Air Pollutants; D035683:MicroRNAs; D005557:Formaldehyde
keywords: epigenetics; formaldehyde; gene expression; inhalation; microRNA.