Regulation of cellular Cyclin D1 gene by arsenic is mediated through miR-2909

M Sharma1, S Sharma, M Arora

  • 1Experimental Medicine & Biotechnology Department, Postgraduate Institute of Medical Education & Research, Chandigarh-160012, India.

Gene
|April 9, 2013
PubMed

Insights

Low-dose arsenic exposure in human cells increases miR-2909, impacting oncogenomics by regulating genes involved in cell cycle control and apoptosis. This discovery reveals a novel epigenomic pathway for arsenic-induced tumors.

Area of Science:

  • * Oncogenomics and Epigenetics
  • * Molecular Biology and Toxicology

Background:

  • * Arsenic is known to influence oncogenomics by regulating genes controlling cell cycle and apoptosis.
  • * The precise molecular mechanisms by which arsenic affects these genes remain unclear.

Purpose of the Study:

  • * To investigate the molecular events linking arsenic exposure to oncogenomic alterations.
  • * To elucidate the role of microRNAs in arsenic-induced gene regulation.

Main Methods:

  • * Exposure of human peripheral blood mononuclear cells (PBMCs) to low concentrations of arsenic.
  • * Analysis of gene and microRNA expression levels, including miR-2909, CCND1, CYLD, SP1, KLF4, AATF, and BCL3.
  • * Investigation of translational and splice-switching regulatory mechanisms.

Main Results:

  • * Arsenic exposure at low concentrations leads to the over-expression of miR-2909 in human PBMCs.
  • * miR-2909 regulates Cyclin D1 (CCND1) gene expression by inducing splice-switching of the CYLD gene.
  • * miR-2909 modulates Specificity Protein 1 (SP1) activity via repression of Kruppel-like factor 4 (KLF4) at the translational level.
  • * Arsenic-induced miR-2909 expression also affects Apoptosis Antagonizing Transcription factor (AATF) and B-cell Lymphoma 3 (BCL3) regulation.

Conclusions:

  • * A novel epigenomic pathway involving miR-2909 is proposed to explain arsenic's role in oncogenomics.
  • * This pathway provides insights into the paradoxical effects of arsenic in cancer development.
  • * The findings may aid in developing strategies for preventing or treating arsenic-induced tumors.

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