title: Fumonisin B₁ modulates expression of human cytochrome P450 1b1 in human hepatoma (Hepg2) cells by repressing Mir-27b.
abstract: Fumonisin B₁ (FB₁), a common mycotoxin contaminant of maize, is known to inhibit sphingolipid biosynthesis and has been implicated in hepatocellular carcinoma promoting activity in humans and animals. MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression via translational repression. Human cytochrome P450 (CYP1B1) is highly expressed in oestrogen target tissues and catalyzes the metabolic activation of many procarcinogens. The aim of our study was to investigate the effect of FB₁ on miR-27b suppression and its effect on CYP1B1 modulation in a human hepatoma cell line (HepG2). MiR27b and CYP1B1 expressions were evaluated in HepG2 cells by quantitative PCR. In order to directly assess the effect of miR-27b on CYP1B1 mRNA levels, cells were transfected with the mimic to miR-27b. CYP1B1 protein expression was measured using Western blot. FB₁ significantly down-regulated (11-fold) expression of miR-27b in HepG2 cells; whilst CYP1B1 mRNA and protein expression was significantly upregulated by 1.8-fold and 2.6-fold, respectively. CYP1B1 is post-transcriptionally regulated by miR-27b after HepG2 exposure to FB₁. FB₁-induced modulation of miR-27b in hepatic cells may be an additional mode of hepatic neoplastic transformation.
authors.affiliation: Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: chutur@ukzn.ac.za.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Chuturgoon
authors.affiliation: Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Alisa
authors.initials: A
authors.lastname: Phulukdaree
authors.affiliation: Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Devapregasan
authors.initials: D
authors.lastname: Moodley
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D016000:Cluster Analysis; D065633:Cytochrome P-450 CYP1B1; D015536:Down-Regulation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects*; D037341:Fumonisins / Q000633:toxicity*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D018716:Molecular Mimicry; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
chemical_list: D002274:Carcinogens, Environmental; D037341:Fumonisins; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C056933:fumonisin B1; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1
keywords: Cytochrome P 450 (CYP1B1); Fumonisin B(1); HepG2 cells; Liver cancer; MicroRNA (miR)-27b