title: miR-21 regulates N-methyl-N-nitro-N'-nitrosoguanidine-induced gastric tumorigenesis by targeting FASLG and BTG2.
abstract: MicroRNAs (miRNAs) are recently discovered regulators of gene expression and are important in the regulation of many cellular events. Evidence collected to date shows that miRNAs are altered after exposure to environmental toxicants. However, the role that miR-21 plays in the gastric tumorigenesis induced by environmental carcinogens remains largely unknown. The aim of this study was to characterize the regulatory role of miR-21 in the carcinogenic processes following exposure to the N-nitroso carcinogen N-methyl-N-nitro-N'-nitrosoguanidine (MNNG). We found a progressive dose- and time-dependent increase in miR-21 expression following treatment with MNNG. Dysregulated miR-21 affected both cell growth in GES-1 cells and the gastric tumorigenesis induced with MNNG. These data demonstrate the involvement of miR-21 in the malignant transformation and tumorigenesis activated by MNNG. We also established that the Fas ligand (FASLG) and B-cell translocation gene 2 (BTG2), regulated by miR-21, contribute to the transformation induced by MNNG in GES-1 cells. This is the first study to show that miR-21 is involved in chemical carcinogenesis in vivo and in vitro. The regulation by miR-21 of the gastric carcinogenesis induced by MNNG highlights the functional roles of miRNAs in chemical carcinogenesis, and offers a new explanation of the mechanisms underlying chemical carcinogenesis.
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of Chinese People's Liberation Army, Guangzhou 510010, PR China.
authors.forename: Enwu
authors.initials: E
authors.lastname: Xu
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Dai
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Shaozhu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Baoying
authors.initials: B
authors.lastname: Peng
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, PR China. Electronic address: jiangyiguo@vip.163.com.
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D002273:Carcinogens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017874:Immediate-Early Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D008769:Methylnitronitrosoguanidine; C070114:BTG2 protein, human
keywords: Gastric cancer; MNNG; MicroRNA; Tumorigenesis; miR-21