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E4BP4/NFIL3 modulates the epigenetically repressed RAS effector RASSF8 function through histone methyltransferases

Isai Pratha Karthik1, Pavitra Desai1, Sudarkodi Sukumar1

  • 1From the Laboratory of Molecular Virology, National Cancer Tissue Biobank, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai 600 036, India and.

The Journal of Biological Chemistry
|February 23, 2018
PubMed

Insights

E4BP4 represses tumor suppressor RASSF8 expression via epigenetic mechanisms involving G9a and SUV39H1. This finding offers insights into breast cancer progression and potential therapeutic targets.

Area of Science:

  • Molecular Oncology
  • Epigenetics
  • Cancer Biology

Background:

  • RAS proteins are key oncogenes, with nonenzymatic RAS effectors (RASSF family) exhibiting tumor-suppressive roles.
  • While most RASSF members are epigenetically silenced by hypermethylation, RASSF8 downregulation mechanisms in cancer remain unclear.

Purpose of the Study:

  • To elucidate the mechanism of RASSF8 downregulation in cancer.
  • To identify transcriptional modulators and epigenetic factors affecting RASSF8 expression.

Main Methods:

  • Investigated the role of E4BP4 in regulating RASSF8 expression.
  • Assessed the involvement of histone methyltransferases G9a and SUV39H1.
  • Correlated RASSF8 and E4BP4 expression in breast tumor samples.

Main Results:

  • Identified E4BP4 as a transcriptional repressor of RASSF8.
  • Demonstrated that E4BP4 utilizes G9a and SUV39H1 to repress RASSF8 expression.
  • Observed a negative correlation between RASSF8 and E4BP4 in breast tumors.
  • Showed E4BP4 antagonizes RASSF8's anti-proliferative and pro-apoptotic effects.

Conclusions:

  • E4BP4 epigenetically represses RASSF8 expression through histone methyltransferases.
  • This mechanism contributes to RASSF8 downregulation in breast cancer.
  • Findings provide insights into RASSF8 regulation and suggest therapeutic strategies.
Keywords:
E4BP4G9aRASSF8Ras proteinSUV39H1apoptosisbreast cancercell proliferationhistone methylationtumor cell biologytumor suppressor gene

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