title: miR-34a screened by miRNA profiling negatively regulates Wnt/β-catenin signaling pathway in Aflatoxin B1 induced hepatotoxicity.
abstract: Aflatoxin-B1 (AFB1), a hepatocarcinogenic mycotoxin, was demonstrated to induce the high rate of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in the regulation of several biological processes in HCC. However, the function of miRNAs in AFB1-induced HCC has received a little attention. Here, we applied Illumina deep sequencing technology for high-throughout profiling of microRNAs in HepG2 cells lines after treatment with AFB1. Analysis of the differential expression profile of miRNAs in two libraries, we identified 9 known miRNAs and 1 novel miRNA which exhibited abnormal expression. KEGG analysis indicated that predicted target genes of differentially expressed miRNAs are involved in cancer-related pathways. Down-regulated of Drosha, DGCR8 and Dicer 1 indicated an impairment of miRNA biogenesis in response to AFB1. miR-34a was up-regulated significantly, down-regulating the expression of Wnt/β-catenin signaling pathway by target gene β-catenin. Anti-miR-34a can significantly relieved the down-regulated β-catenin and its downstream genes, c-myc and Cyclin D1, and the S-phase arrest in cell cycle induced by AFB1 can also be relieved. These results suggested that AFB1 might down-regulate Wnt/β-catenin signaling pathway in HepG2 cells by up-regulating miR-34a, which may involve in the mechanism of liver tumorigenesis.
authors.affiliation: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, 100083.
authors.forename: Liye
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Beijing Laboratory for Food Quality and Safety, Beijing, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, 100083.|Beijing Laboratory for Food Quality and Safety, Beijing, P. R. China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: Huang
authors.affiliation: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, 100083.|Beijing Laboratory for Food Quality and Safety, Beijing, P. R. China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, 100083.
authors.forename: Boyang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, 100083.|Beijing Laboratory for Food Quality and Safety, Beijing, P. R. China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Xu
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D017423:Sequence Analysis, RNA; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: C474043:DGCR8 protein, human; C522425:MIRN34 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051176:beta Catenin; D019938:Cyclin D1; D016604:Aflatoxin B1; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases