Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
Toxicol Lett. 2014 May 16;227(1):50-5. doi: 10.1016/j.toxlet.2014.02.026. Epub 2014 Mar 12.
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.
伏马菌素 B₁（FB₁）是一种常见的玉米真菌毒素污染物，已知其抑制鞘脂类生物合成，并与人类和动物的肝癌促进活性有关。microRNAs（miRNA）是通过翻译抑制来调节基因表达的小非编码 RNA。人细胞色素 P450（CYP1B1）在雌激素靶组织中高度表达，并催化许多前致癌物的代谢活化。我们的研究目的是研究 FB₁对 miR-27b 抑制的影响及其对人肝癌细胞系（HepG2）中 CYP1B1 调节的影响。通过定量 PCR 评估 HepG2 细胞中 miR27b 和 CYP1B1 的表达。为了直接评估 miR-27b 对 CYP1B1 mRNA 水平的影响，用 miR-27b 模拟物转染细胞。使用 Western blot 测量 CYP1B1 蛋白表达。FB₁ 显著下调（11 倍）HepG2 细胞中 miR-27b 的表达；而 CYP1B1 mRNA 和蛋白表达分别上调 1.8 倍和 2.6 倍。CYP1B1 在后转录水平受到 HepG2 暴露于 FB₁ 后 miR-27b 的调节。FB₁ 诱导的肝细胞中 miR-27b 调节可能是肝肿瘤转化的另一种模式。
