Aberrant Expression of miR-638 Contributes to Benzo(a)pyrene-Induced Human Cell Transformation

• DOI: 10.1093/toxsci/kfr299
• Publication Date: 2011-11-03T00:37:09Z
• Authors: Daochuan Li; Qing Wang; Caixia Liu; Huawei Duan; Xiaowen Zeng; Bo Zhang; Xiaodong Li; Jian Zhao; Shifu Tang; Zhifang Li; Xiumei Xing; Ping Yang; Liping Chen; Junling Zeng; Xiaonian Zhu; Shixin Zhang; Zhengbao Zhang; Lu Ma; Zhini He; Erman Wang; Yongmei Xiao; Yuxin Zheng; Wen Chen
• Keywords: Genetic Markers; Male; 0301 basic medicine; China; Lung Neoplasms; Dose-Response Relationship, Drug; BRCA1 Protein; Gene Expression Profiling; Epithelial Cells; 3. Good health; 03 medical and health sciences; Cell Transformation, Neoplastic; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Cell Line, Tumor; Benzo(a)pyrene; Carcinogens; Humans; Lymphocytes; Biomarkers; Biotransformation; Cell Line, Transformed; DNA Damage

Identification of aberrant microRNA (miRNA) expression during chemical carcinogen–induced cell transformation will lead to a better understanding the substantial role miRNAs in cancer development. To explore whether can be used as biomarkers exposure risk assessment carcinogenesis, we analyzed miRNA profiles human bronchial epithelial cells expressing an oncogenic allele H-Ras (HBER) at different stages induced by benzo(a)pyrene (BaP) array. It revealed 12 differentially expressed HBER both pretransformed and transformed stages. Differentially were confirmed examined 50 pairs primary non–small-cell lung (NSCLC) tissues using real-time PCR. Among these miRNAs, downregulation miR-638 was found 68% (34/50) NSCLC tissues. However, increased upon treatment BaP dose-dependent manner. The also peripheral lymphocytes from 86 polycyclic aromatic hydrocarbons (PAHs)-exposed (PE) workers. We that average level PE workers 72% compared with control group. levels correlated concentration urinary 1-hydroxypyrene (1-OHP) external PAHs. Overexpression aggravated DNA damage BaP, which might mediated suppression breast 1 (BRCA1), one target genes miR-638. In summary, suggest is involved BaP-induced carcinogenesis targeting BRCA1.