Cancer Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University , Durham, NC, USA.
Bioinformatics Research Center, Ricks Hall, 1 Lampe Dr, North Carolina State University , Raleigh, NC, USA.
Epigenetics. 2021 Mar;16(3):289-299. doi: 10.1080/15592294.2020.1795601. Epub 2020 Jul 27.
Studies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour progression and is additionally associated with decreased DNA methylation. The expression of , methyltransferases, and was assessed in prostate cancer cells (LNCaP) treated with EGF, an EGFR inhibitor PD16893, and the methyltransferase inhibitor, 5-azacytidine, respectively. The results showed that EGF treatment decreased levels of expression of all four genes and that their expression was reversed by PD16893. Treatment with 5-azacytidine, markedly decreased expression of and over 85% as well as significantly decreased expression of , but not the expression of siRNA treated LNCaP cells had decreased expression of and , while siRNA treated cells had only moderately decreased expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased expression. Additionally, methylation differences between prostate cancer samples and benign prostate samples from an Illumina 450K Methylation Array study were assessed. The results taken together suggest that hypomethylation of the and genes contributes to increased risk of prostate cancer and may provide a putative biomarker or epigenetic target for chemotherapeutics. Mechanistic studies are warranted to determine the role of the methylation marks in prostate cancer.
研究表明，解毒酶 UGT2B15 和 UGT2B17 的表达缺失与前列腺肿瘤的风险和进展有关。我们研究了 EGF 对这些酶表达的作用，因为它与信号通路相互作用，也会影响前列腺肿瘤的进展，并且与 DNA 甲基化减少有关。我们用 EGF、EGFR 抑制剂 PD16893 和甲基转移酶抑制剂 5-氮杂胞苷分别处理前列腺癌细胞（LNCaP），评估了 UGT2B15、UGT2B17、 和 甲基转移酶的表达。结果表明，EGF 处理降低了这四个基因的表达水平，而 PD16893 逆转了它们的表达。5-氮杂胞苷处理显著降低了 和 超过 85%的表达，显著降低了 的表达，但不降低 的表达。用 siRNA 处理的 LNCaP 细胞的 和 表达降低，而 siRNA 处理的细胞仅中度降低 的表达。DNMT 甲基转移酶抑制剂 RG108 的处理显著降低了 的表达。此外，还评估了来自 Illumina 450K 甲基化阵列研究的前列腺癌样本和良性前列腺样本之间的甲基化差异。综合结果表明， 和 基因的低甲基化导致前列腺癌风险增加，并且可能为化疗药物提供潜在的生物标志物或表观遗传靶标。有必要进行机制研究，以确定甲基化标记在前列腺癌中的作用。
