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Published on: August 5, 2022

Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced tumorigenesis

Jing Zhang1, Yang Zhou, You-Jun Wu

  • 1Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; School of Life Science and Technology, Tongji University, Shanghai 200092, China.

Toxicology Letters
|August 24, 2013
PubMed

Insights

Nickel-induced cancer development involves the silencing of tumor suppressor microRNAs (miRNAs). DNA methylation causes downregulation of miR-203, a key factor in nickel carcinogenesis.

Area of Science:

  • Environmental Toxicology
  • Molecular Carcinogenesis
  • Epigenetics

Background:

  • Nickel compounds are known carcinogens, with epigenetic mechanisms like DNA methylation implicated in their cancer-causing effects.
  • MicroRNAs (miRNAs) are increasingly recognized for their roles in carcinogenesis, potentially acting as tumor suppressors or oncogenes.

Purpose of the Study:

  • To investigate the role of specific microRNAs (miRNAs) in nickel-induced carcinogenesis.
  • To elucidate the mechanism by which nickel affects miRNA expression and contributes to tumor development.

Main Methods:

  • Utilized Ni3S2-transformed 16HBE cells (NSTCs) to study nickel-induced cellular changes.
  • Analyzed miRNA expression profiles, focusing on potential tumor suppressors.
  • Investigated DNA methylation patterns in the promoter and first exon of downregulated miRNAs.
  • Identified target genes regulated by the affected miRNAs.

Main Results:

  • Observed significant downregulation of miR-203 in nickel-transformed cells.
  • Found hypermethylation in the promoter and first exon of miR-203, correlating with its reduced expression.
  • Demonstrated that miR-203 negatively regulates ABL1, a gene potentially involved in tumorigenesis.
  • Established a link between DNA methylation-associated silencing of miR-203 and nickel-induced cancer development.

Conclusions:

  • DNA methylation-driven silencing of tumor suppressor miRNAs, specifically miR-203, is a key event in nickel-induced carcinogenesis.
  • miR-203 acts as a suppressor of nickel-induced tumorigenesis, partly by regulating ABL1.
  • Epigenetic modifications of miRNAs represent a critical pathway in the development of cancers associated with nickel exposure.
Keywords:
ABL1HypermethylationNSTCsNi(3)S(2)-transformed 16HBE cellsNickelTumorigenesismiR-203

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