Expression of UDP Glucuronosyltransferases <i>2B15</i> and <i>2B17</i> is associated with methylation status in prostate cancer cells

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 <i>UGT2B15, UGT2B17</i>, <i>de novo</i> methyltransferases, <i>DNMT3A</i> and <i>DNMT3B</i> 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 <i>UGT2B15</i> and <i>UGT2B17</i> over 85% as well as significantly decreased expression of <i>DNMT3B</i>, but not the expression of <i>DNMT3A. DNMT3B</i> siRNA treated LNCaP cells had decreased expression of <i>UGT2B15</i> and <i>UGT2B17</i>, while <i>DNMT3A</i> siRNA treated cells had only moderately decreased <i>UGT2B15</i> expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased <i>UGT2B17</i> 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 <i>UGT2B15</i> and <i>UGT2B17</i> 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.

已有研究表明，解毒酶UDP-葡糖醛酸转移酶2B15（UGT2B15）与UDP-葡糖醛酸转移酶2B17（UGT2B17）的表达缺失与前列腺肿瘤的发病风险及进展密切相关。本研究探究了表皮生长因子（Epidermal Growth Factor, EGF）对这两种酶表达的调控作用：因其可通过与信号通路相互作用影响前列腺肿瘤进展，且与DNA甲基化水平降低相关。
我们分别用EGF、表皮生长因子受体（Epidermal Growth Factor Receptor, EGFR）抑制剂PD16893以及甲基转移酶抑制剂5-氮胞苷（5-azacytidine）处理前列腺癌细胞（LNCaP），并检测其中UGT2B15、UGT2B17、从头型DNA甲基转移酶DNMT3A（DNA methyltransferase 3A）及DNMT3B（DNA methyltransferase 3B）的表达水平。
结果显示，EGF处理可降低这四个基因的表达水平，且该抑制效应可被PD16893逆转。5-氮胞苷处理可显著下调UGT2B15与UGT2B17的表达（降幅超85%），同时显著降低DNMT3B的表达，但对DNMT3A的表达无显著影响。使用DNMT3B小干扰RNA（small interfering RNA, siRNA）处理LNCaP细胞后，UGT2B15与UGT2B17的表达水平降低；而使用DNMT3A siRNA处理的细胞中，UGT2B15的表达仅出现中度下调。使用DNA甲基转移酶抑制剂RG108处理后，UGT2B17的表达水平显著降低。
此外，我们基于Illumina 450K甲基化芯片（Illumina 450K Methylation Array）研究的数据，分析了前列腺癌组织与良性前列腺组织之间的甲基化差异。综合以上结果可知，UGT2B15与UGT2B17基因的低甲基化会增加前列腺癌的发病风险，且可作为潜在的生物标志物或化疗表观遗传靶点。未来仍需开展机制研究，以明确甲基化标记在前列腺癌中的具体作用。

搜集汇总

背景与挑战

背景概述

该数据集研究前列腺癌细胞中UGT2B15和UGT2B17的表达与DNA甲基化状态的关联，通过实验处理（如EGF、抑制剂）和甲基化阵列分析，发现这些基因的低甲基化可能增加前列腺癌风险，并作为潜在的生物标志物或表观遗传治疗靶点。数据集包括实验数据和甲基化分析结果，涉及生物化学、医学和遗传学等多个学科领域。