Experimental Pharmacology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy.
Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Brescia, Italy.
Sci Rep. 2018 Jul 10;8(1):10395. doi: 10.1038/s41598-018-28739-6.
Arsenic and arsenic-derivative compounds, named as arsenicals, represent a worldwide problem for their effect on the human health and, in particular, for their capability to increase the risk of developing cancer such as kidney, bladder and prostate cancer. The main source of arsenical exposure is drinking water. Nowadays, it is well known that the chronic exposure to arsenicals leads to a series of epigenetic alterations that have a role in arsenic-induced effects on human health including cancer. Based on these observations, the aim of our study was to select by network analysis the genes/proteins/miRNAs implicated in kidney, bladder and prostate cancer development upon arsenical exposure. From this analysis we identified: (i) the nodes linking the three molecular networks specific for kidney, bladder and prostate cancer; (ii) the relative HUB nodes (RXRA, MAP3K7, NR3C1, PABPC1, NDRG1, RELA and CTNNB1) that link the three cancer networks; (iii) the miRNAs able to target these HUB nodes. In conclusion, we highlighted a panel of potential molecules related to the molecular mechanisms of arsenical-induced cancerogenesis and suggest their utility as biomarkers or therapeutic targets.
砷和砷的衍生物化合物，被称为砷剂，对人类健康有影响，特别是会增加患癌症的风险，如肾癌、膀胱癌和前列腺癌，这是一个全球性的问题。砷剂暴露的主要来源是饮用水。如今，人们已经清楚地认识到，慢性砷暴露会导致一系列表观遗传改变，这些改变在砷对人类健康的影响（包括癌症）中起作用。基于这些观察结果，我们的研究目的是通过网络分析选择在砷暴露下参与肾癌、膀胱癌和前列腺癌发展的基因/蛋白质/miRNA。通过这项分析，我们确定了：（i）连接三种特定于肾癌、膀胱癌和前列腺癌的分子网络的节点；（ii）连接三种癌症网络的相对 HUB 节点（RXRA、MAP3K7、NR3C1、PABPC1、NDRG1、RELA 和 CTNNB1）；（iii）能够靶向这些 HUB 节点的 miRNAs。总之，我们强调了一组与砷诱导的癌症发生的分子机制相关的潜在分子，并提出了将其用作生物标志物或治疗靶点的建议。
