miR-106a-mediated malignant transformation of cells induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide.
microRNAs (miRNAs) are an abundant class of small noncoding RNAs that function primarily as oncogenes and tumor suppressors by mediating translational repression or mRNA degradation via binding target genes. In this study, malignant human bronchial epithelial cells transformed by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide were used to help characterize the possible mechanisms of miRNA function in chemical carcinogenesis. The expression level of miR-106a was measured by the real-time, reverse transcriptase polymerase chain reaction. We used the miR-106a inhibitor and the miR-106a mimic to downregulate or upregulate miR-106a activity in malignantly transformed cells to determine the effects of miR-106a on the biological properties of the cell. We observed overrepresentation of miR-106a in transformed cells compared with control cells. Silencing miR-106a by transfection with the miR-106a inhibitor suppressed cell proliferation, induced cell cycle arrest and apoptosis, and inhibited anchorage-independent growth and tumor growth in nude mice. Increasing miR-106a in malignantly transformed cells by transfection with the miR-106a mimic gave the opposite results. Moreover, untransformed cells showed a reduction of cell cycle arrest and apoptosis rate followed by transfection with the miR-106a mimic. Bioinformatic analysis showed that tumor suppressor RB1 is one of predictive targets of miR-106a. We confirmed this target by Western blot and dual luciferase assay. Our findings suggest that miR-106a might function as an oncogene in transformation induced by a chemical carcinogen. Thus, knock down of miR-106a in malignant cells is a potential therapeutic strategy.
Jiang
Yiguo
Y
Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182, People's Republic of China. jiangyiguo@yahoo.com
Wu
Yan
Y
Greenlee
Anne R
AR
Wu
Jianjun
J
Han
Zhiyuan
Z
Li
Xun
X
Zhao
Yao
Y
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
D002273:Carcinogens; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D016160:Retinoblastoma Protein; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide