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RNPC1, an RNA-binding protein and a p53 target, regulates macrophage inhibitory cytokine-1 (MIC-1) expression through

Tiffany Yin1, Seong-Jun Cho, Xinbin Chen

  • 1Comparative Oncology Laboratory, University of California, Davis, California 95616, USA.

The Journal of Biological Chemistry
|July 10, 2013
PubMed

Insights

Macrophage inhibitory cytokine-1 (MIC-1) levels are regulated by RNA-binding protein RNPC1. RNPC1 enhances MIC-1 mRNA stability, influencing cell growth and potentially cancer progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Macrophage inhibitory cytokine-1 (MIC-1) is a secreted cytokine involved in cell proliferation, apoptosis, metastasis, and angiogenesis.
  • Serum MIC-1 levels correlate with cancer progression, suggesting diagnostic potential.
  • MIC-1 exhibits dual roles in cancer, acting as both a tumor suppressor and promoter.

Purpose of the Study:

  • To investigate post-transcriptional regulation mechanisms of MIC-1.
  • To elucidate the role of RNA-binding protein RNPC1 in controlling MIC-1 expression.
  • To understand how RNPC1 influences MIC-1's function in cell growth.

Main Methods:

  • Overexpression and knockdown/knock-out of RNPC1 in cellular models.
  • RNA-binding protein immunoprecipitation followed by quantitative PCR (RIP-qPCR) to assess RNPC1-MIC-1 mRNA interaction.
  • Analysis of MIC-1 mRNA stability using techniques like actinomycin D treatment.
  • Cell growth assays following manipulation of MIC-1 and RNPC1 levels.

Main Results:

  • RNPC1 overexpression increased MIC-1 transcript and protein levels, while RNPC1 knockdown/knock-out decreased them.
  • RNPC1 directly binds to MIC-1 mRNA, specifically to an AU-rich element in the 3'-untranslated region (3'-UTR).
  • RNPC1 binding enhances MIC-1 mRNA stability.
  • Knockdown of MIC-1 abrogated RNPC1-induced cell growth suppression.

Conclusions:

  • RNPC1 is a novel regulator of MIC-1 expression, primarily through enhancing mRNA stability.
  • This RNPC1-mediated regulation of MIC-1 impacts cell growth.
  • The findings reveal a new layer of MIC-1 control beyond transcriptional regulation, with implications for understanding cancer biology.
Keywords:
Cell ProliferationGDF-15Gene RegulationMIC-1RNA-binding ProteinRNPC1mRNA Decayp21p53

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