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Gene. 2014 Jan 10;533(2):508-14. doi: 10.1016/j.gene.2013.09.049. Epub 2013 Sep 27.

MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects.

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Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Medicina Genómica y Toxicología Ambiental, C.U., 04510 México, México.


Metals are a threat to human health by increasing disease risk. Experimental data have linked altered miRNA expression with exposure to some metals. MiRNAs comprise a large family of non-coding single-stranded molecules that primarily function to negatively regulate gene expression post-transcriptionally. Although several human populations are exposed to low concentrations of As, Cd and Pb as a mixture, most toxicology research focuses on the individual effects that these metals exert. Thus, this study aims to evaluate global miRNA and mRNA expression changes induced by a metal mixture containing NaAsO2, CdCl2, Pb(C2H3O2)2·3H2O and to predict possible metal-associated disease development under these conditions. Our results show that this metal mixture results in a miRNA expression profile that may be responsible for the mRNA expression changes observed under experimental conditions in which coding proteins are involved in cellular processes, including cell death, growth and proliferation related to the metal-associated inflammatory response and cancer.


ADCYAP1; ATSDR; Agency for Toxic Substances and Disease Registry; Al(2)(SO(4))(3); As; As(2)O(3); Bioinformatics; C-MOS; CA; CAMK2A; CASP3; CCNI; CLCC1; CNN1; CNTD1; CO(2); CYP1A1; California; Cd; CdCl(2); Ct; DE; DHFR; DMEM; DNA; DNAJ (Hsp40) homolog subfamily B member 4; DNAJB4; Delaware; Disease; Dulbecco's modified Eagle's minimum essential medium; EDEM3; EDTA; ER degradation enhancer mannosidase alpha-like 3; FBJ murine osteosarcoma viral oncogene homolog; FBS; FGFR; FGFRL1; FOS; FZD4; FZD6; Fc; Fe(2)SO(4); GLO1; HN; HepG2; Homo sapiens bone osteosarcoma cell line; IPA; Ingenuity Pathway Analysis; KCND2; LAMC1; Log; M. musculus; MADD; MAP-kinase activating death domain; MBNL1; MD; MG63; MGD; MTPN; Maryland; Metal; MicroRNA; Mouse Genome Database; Mus musculus; NCAM1; NDFIP1; NK6 homeobox 1; NKX6-1; NUPL2; NY; NaAsO(2); NaVO(3); New York; NiSO(4); OGDH; PBS; PCR; PGM3; PHACTR2; PLXNA2; PM; PPP2CB; Pb; Pb(C(2)H(3)O(2))(2)·3H(2)O; RAB30; RAB30 member RAS oncogene family; RAP2B; RAP2B member RAS oncogene family; RIPK4; RNA; ROS; RT-qPCR; SDS; SFN; SLC1A1; SMAP1; SP1; SP1 transcription factor; SPAM1; SRXN1; STAG2; STAT3; STK4; T lymphocyte cell line; T4; TK6; TLDA; TaqMan low density array; TiO(2); UTR; WI; Wisconsin; ZrO(2); adenylate cyclase activating polypeptide 1; aluminium sulfate; arsenic; arsenic trioxide; cDNA; cadmium; cadmium chloride; calcium/calmodulin-dependent protein kinase II alpha; calponin 1; carbon dioxide; caspase 3; chloride channel CLIC-like 1; complementary deoxyribonucleic acid; cycle threshold; cyclin I; cyclin N-terminal domain containing 1; cytochrome P450 family 1 subfamily A polypeptide 1; degree Celsius; deoxyribonucleic acid; dihydrofolate reductase; ethylenediaminetetraacetic acid; fetal bovine serum; fibroblast growth factor receptor; fibroblast growth factor receptor-like 1; fold change; frizzled family receptor 4; frizzled family receptor 6; glyoxalase I; h; hour; human hepatocellular G2 cell line; human neural glioma cell line; iron sulfate; laminin gamma 1; lead; lead acetate; logarithm; mRNA; messenger RNA; miRNA; microRNA; micromolar; moloney murine sarcoma oncogene; muscleblind-like splicing regulator 1; myotrophin; nM; nanomolar; nedd4 family interacting protein 1; neural cell adhesion molecule 1; nickel sulfate; nucleoporin like 2; oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide); p-value; particulate matter; phosphatase and actin regulator 2; phosphate-buffered saline; phosphoglucomutase 3; plexin A2; polymerase chain reaction; potassium voltage-gated channel Shal-related subfamily member 2; probability value; protein phosphatase 2 catalytic subunit beta isozyme; reactive oxygen species; receptor-interacting serine–threonine kinase 4; reverse transcription quantitative polymerase chain reaction; ribonucleic acid; serine dehydratase; serine/threonine kinase 4; signal transducer and activator of transcription 3; small ArfGAP 1; sodium meta-arsenite; sodium vanadate; solute carrier family 1 member 1; sperm adhesion molecule 1; stratifin; stromal antigen 2; sulfiredoxin 1; thymidine kinase 6 cell line; titanium dioxide; untranslated region; zirconium dioxide; °C; μM

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