title: Aberrant expression of miR-638 contributes to benzo(a)pyrene-induced human cell transformation.
abstract: Identification of aberrant microRNA (miRNA) expression during chemical carcinogen-induced cell transformation will lead to a better understanding of the substantial role of miRNAs in cancer development. To explore whether aberrant miRNAs expression can be used as biomarkers of chemical exposure in risk assessment of chemical carcinogenesis, we analyzed miRNA expression profiles of human bronchial epithelial cells expressing an oncogenic allele of H-Ras (HBER) at different stages of transformation induced by benzo(a)pyrene (BaP) by miRNA array. It revealed 12 miRNAs differentially expressed in HBER cells at both pretransformed and transformed stages. Differentially expressed miRNAs were confirmed in transformed cells and examined in 50 pairs of primary human non-small-cell lung cancer (NSCLC) tissues using real-time PCR. Among these miRNAs, downregulation of miR-638 was found in 68% (34/50) of NSCLC tissues. However, the expression of miR-638 in HBER cells increased upon treatment of BaP in a dose-dependent manner. The expression of miR-638 was also examined in peripheral lymphocytes from 86 polycyclic aromatic hydrocarbons (PAHs)-exposed (PE) workers. We found that the average expression level of miR-638 in peripheral lymphocytes from 86 PE workers increased by 72% compared with control group. The levels of miR-638 were correlated with the concentration of urinary 1-hydroxypyrene (1-OHP) and external levels of PAHs. Overexpression of miR-638 aggravated cell DNA damage induced by BaP, which might be mediated by suppression of breast cancer 1 (BRCA1), one of the target genes of miR-638. In summary, we suggest that miR-638 is involved in the BaP-induced carcinogenesis by targeting BRCA1.
authors: Department of Toxicology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
authors: Daochuan
authors: D
authors: Li
authors: Qing
authors: Q
authors: Wang
authors: Caixia
authors: C
authors: Liu
authors: Huawei
authors: H
authors: Duan
authors: Xiaowen
authors: X
authors: Zeng
authors: Bo
authors: B
authors: Zhang
authors: Xiaodong
authors: X
authors: Li
authors: Jian
authors: J
authors: Zhao
authors: Shifu
authors: S
authors: Tang
authors: Zhifang
authors: Z
authors: Li
authors: Xiumei
authors: X
authors: Xing
authors: Ping
authors: P
authors: Yang
authors: Liping
authors: L
authors: Chen
authors: Junling
authors: J
authors: Zeng
authors: Xiaonian
authors: X
authors: Zhu
authors: Shixin
authors: S
authors: Zhang
authors: Zhengbao
authors: Z
authors: Zhang
authors: Lu
authors: L
authors: Ma
authors: Zhini
authors: Z
authors: He
authors: Erman
authors: E
authors: Wang
authors: Yongmei
authors: Y
authors: Xiao
authors: Yuxin
authors: Y
authors: Zheng
authors: Wen
authors: W
authors: Chen
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D002681:China; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D016273:Occupational Exposure; D020411:Oligonucleotide Array Sequence Analysis; D011721:Pyrenes / Q000378:metabolism; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D015415:Biomarkers; D002273:Carcinogens; D005819:Genetic Markers; C572154:MIRN638 microRNA, human; D035683:MicroRNAs; D011721:Pyrenes; D001564:Benzo(a)pyrene; C033146:1-hydroxypyrene