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Tumor suppression by RNA from C/EBPβ 3'UTR through the inhibition of protein kinase Cε activity

Ying Wang1, Da-Quan Sun, Ding-Gan Liu

  • 1State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Plos One
|February 2, 2011
PubMed
Abstract

Insights

Short RNAs from the C/EBPβ 3'untranslated region (3'UTR) suppress tumors by inhibiting protein kinase Cε. This C/EBPβ 3'UTR RNA directly binds and reduces protein kinase Cε activity, impacting keratin 18 phosphorylation and expression in hepatocarcinoma cells.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • The 3'untranslated region (3'UTR) of eukaryotic mRNAs can contain sequences with tumor suppressor activity.
  • Short RNAs derived from the 3'UTR of C/EBPβ mRNA have shown potential in inhibiting cancer cell growth.

Purpose of the Study:

  • To elucidate the molecular mechanism behind the tumor suppression activity of C/EBPβ 3'UTR RNA in human hepatocarcinoma cells (SMMC-7721).

Main Methods:

  • Western blotting
  • Immunocytochemistry
  • Molecular beacon assays
  • Confocal microscopy
  • Protein kinase inhibitors
  • In vitro kinase assays

Main Results:

  • C/EBPβ 3'UTR RNA induced reorganization of keratin 18 by binding to it.
  • This RNA reduced keratin 18 phosphorylation and expression.
  • Protein kinase Cε was identified as the enzyme responsible for keratin 18 phosphorylation.
  • C/EBPβ 3'UTR RNA directly inhibited protein kinase Cε activity and bound to the protein kinase Cε-keratin 18 complex.

Conclusions:

  • Tumor suppression by C/EBPβ 3'UTR RNA in SMMC-7721 cells is mediated by inhibiting protein kinase Cε activity via direct physical interaction.
  • This suggests that 3'UTR sequences can act as regulatory elements for genes beyond their own mRNA.

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