title: Long non-coding RNAs as novel expression signatures modulate DNA damage and repair in cadmium toxicology.
abstract: Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in a variety of physiological and pathophysiological processes. Our study was to investigate whether lncRNAs as novel expression signatures are able to modulate DNA damage and repair in cadmium(Cd) toxicity. There were aberrant expression profiles of lncRNAs in 35th Cd-induced cells as compared to untreated 16HBE cells. siRNA-mediated knockdown of ENST00000414355 inhibited the growth of DNA-damaged cells and decreased the expressions of DNA-damage related genes (ATM, ATR and ATRIP), while increased the expressions of DNA-repair related genes (DDB1, DDB2, OGG1, ERCC1, MSH2, RAD50, XRCC1 and BARD1). Cadmium increased ENST00000414355 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood ENST00000414355 expression and urinary/blood Cd concentrations, and there were significant correlations of lncRNA-ENST00000414355 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. These results indicate that some lncRNAs are aberrantly expressed in Cd-treated 16HBE cells. lncRNA-ENST00000414355 may serve as a signature for DNA damage and repair related to the epigenetic mechanisms underlying the cadmium toxicity and become a novel biomarker of cadmium toxicity.
authors.affiliation: School of Public Health, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: School of Public Health, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
authors.forename: Haibai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine of Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, P.R. China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shenzhen Longgang District Center for Disease Control &Prevention, Shenzhen 518108, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: School of Public Health, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
authors.forename: Qinhai
authors.initials: Q
authors.lastname: Huang
authors.affiliation: School of Public Health, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
authors.forename: Chanjiao
authors.initials: C
authors.lastname: Zheng
authors.affiliation: School of Public Health, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Lei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D019295:Computational Biology; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C091435:DDB1 protein, human; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D062085:RNA, Long Noncoding; D002104:Cadmium; D064007:Ataxia Telangiectasia Mutated Proteins; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human