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This study aimed to investigate whether long noncoding RNA (LncRNA)\u2013ENST00000446135 could serve as a novel biomarker of Cd toxicity in cells, animals, and Cd-exposed workers and regulate DNA damage and repair. LncRNA\u2013ENST00000446135 expression increased gradually in cadmium chloride-transformed 16HBE cells. Small interfering RNA-mediated knockdown of LncRNA\u2013ENST00000446135 inhibited the growth of DNA-damaged cells and decreased the expressions of DNA damage-related genes (ATM, ATR, and ATRIP), whereas increased the expressions of DNA repair-related genes (DDB1, DDB2, OGG1, ERCC1, MSH2, XRCC1, and BARD1). Chromatin immunoprecipitation-sequencing showed that MSH2 is a direct transcriptional target of lncRNA\u2013ENST00000446135. Cadmium increased lncRNA\u2013ENST00000446135 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood ENST00000446135 expression and urinary\/blood Cd concentrations, and there were significant correlations of LncRNA\u2013ENST00000446135 expression with the DNA damage cell and the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd-exposed workers and significantly correlated with liver and renal function in Cd-exposed workers. These results indicate that the expression of LncRNA\u2013ENST00000446135 is upregulated and 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.<\/jats:p>","DOI":"10.1093\/toxres\/tfaa088","type":"journal-article","created":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T12:07:32Z","timestamp":1604232452000},"page":"823-834","source":"Crossref","is-referenced-by-count":16,"title":["LncRNA\u2013ENST00000446135 is a novel biomarker of cadmium toxicity in 16HBE cells, rats, and Cd-exposed workers and regulates DNA damage and repair"],"prefix":"10.1093","volume":"9","author":[{"given":"Zhiheng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of General Practice, Shenzhen Futian Second People\u2019s Hospital, Shenzhen 518040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Health Management, Guangzhou Huali Science and Technology Vocational College, Guangzhou 511325, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chronic Non-communicable Disease Prevention and Control, Futian Hospital for Prevention and Treatment of Chronic Disease, Shenzhen 518048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Disinsecticidal, Shenzhen Longang District Center for Disease Control and Prevention, Shenzhen 518172, P.R. 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