title: miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1.
abstract: Environmental carcinogens-induced lung cancer and potential mechanisms have attracted widespread attention. Currently, microRNAs (miRNAs) have been recognized as key players in development of cancer, among which guide strand of miRNA has been well documented rather than its passenger strand (miRNA*). Our previous study showed that treatment of 0.1 nM AFB1 for 50 passages could induce malignant transformation of immortalized human bronchial epithelial cells stably expressing CYP2A13 (P50 B-2A13 cells). However, the role of miRNAs in this carcinogenic proceeding is still unclear. In present study, 36 upregulated and 27 downregulated miRNAs in P50 B-2A13 cells were first identified by miRNA microarray, and miR-138-1* was selected as a candidate miRNA by RT-qPCR and pilot experiments. Functional studies revealed that miR-138-1* could inhibit proliferation, colony formation, migration and invasion of P50 B-2A13 cells. Further, target analysis and dual-luciferase reporter gene assay identified that miR-138-1(*) was consequentially paired with 3'-UTR of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and decreased the luciferase activity. miR-138-1* could decrease the expressions of PDK1 and its downstream proteins in PI3K/PDK/Akt pathway but not vice versa, indicating that miR-138-1* might affect AFB1-induced malignant transformation through targeting PDK1. As predicted, interference of PDK1 showed the similar effects to miR-138-1* in the proliferation, colony formation, migration and invasion of P50 B-2A13 cells. Our study demonstrated that miR-138-1* played a critical role in AFB-induced malignant transformation of B-2A13 cells by targeting PDK1. Still, the study provides a novel insight into the roles of miRNA* during carcinogenesis, particularly airborne carcinogens-induced lung cancer.
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.|State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, People's Republic of China.|Department of Preventive Medicine, Bengbu Medical College, 2600 Donghai Avenue, Bengbu, 233030, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.|State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, People's Republic of China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.
authors.forename: Huanqiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Ji
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.
authors.forename: Hengsen
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.|State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Environmental Toxicology, Institute of Environmental and Human Health, Texas Tech University, 1207 Gilbert Drive, Lubbock, TX, 79416, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Gao
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. wangshl@njmu.edu.cn.|State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, People's Republic of China. wangshl@njmu.edu.cn.
authors.forename: Shou-Lin
authors.initials: SL
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016604:Aflatoxin B1 / Q000378:metabolism / Q000633:toxicity*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D016604:Aflatoxin B1; D001189:Aryl Hydrocarbon Hydroxylases; C414206:CYP2A13 protein, human; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human
keywords: 3-Phosphoinositide-dependent protein kinase-1 (PDK1); Aflatoxin B1; BEAS-2B cells; Cytochrome P450 2A13; Malignant transformation; miR-138-1*