Identifying a panel of genes/proteins/miRNAs modulated by arsenicals in bladder, prostate, kidney cancers

Sci Rep. 2018 Jul 10;8(1):10395. doi: 10.1038/s41598-018-28739-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arsenicals / chemistry
  • Cell Cycle Proteins / genetics
  • Disease-Free Survival
  • Drinking Water / chemistry
  • Epigenesis, Genetic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kidney Neoplasms / chemically induced
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • MAP Kinase Kinase Kinases / genetics
  • Male
  • MicroRNAs / genetics
  • Poly(A)-Binding Proteins / genetics
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Receptors, Glucocorticoid / genetics
  • Retinoid X Receptor alpha / genetics
  • Transcription Factor RelA / genetics
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • beta Catenin / genetics

Substances

  • Arsenicals
  • CTNNB1 protein, human
  • Cell Cycle Proteins
  • Drinking Water
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • N-myc downstream-regulated gene 1 protein
  • NR3C1 protein, human
  • PABPC1L protein, human
  • Poly(A)-Binding Proteins
  • RELA protein, human
  • RXRA protein, human
  • Receptors, Glucocorticoid
  • Retinoid X Receptor alpha
  • Transcription Factor RelA
  • beta Catenin
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7