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Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism

Giulia Antoniali1, Fabrizio Serra1,2, Lisa Lirussi1,3

  • 1Department of Medicine, Laboratory of Molecular Biology and DNA repair, University of Udine, p.le M. Kolbe 4, Udine, 33100, Italy.

Nature Communications
|October 8, 2017
PubMed

Insights

Apurinic/apyrimidinic endonuclease 1 (APE1) is crucial for DNA repair and impacts cancer. This study reveals APE1

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • Apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA repair enzyme.
  • APE1's role in genome stability, oxidative stress, tumor progression, and chemoresistance is established.
  • The precise molecular mechanisms of APE1 in these processes remain incompletely understood.

Purpose of the Study:

  • To elucidate the novel role of APE1 in RNA metabolism.
  • To investigate APE1's interactions with RNA and proteins.
  • To determine APE1's function in microRNA processing and its implications in cancer.

Main Methods:

  • Characterization of APE1 interactomes with RNA and proteins.
  • Analysis of APE1's association with the DROSHA-processing complex.
  • Assessment of APE1's endonuclease activity in microRNA processing.
  • Evaluation of APE1's role in regulating PTEN expression.
  • Analysis of APE1 in cancer patient cohorts.

Main Results:

  • APE1 is involved in pri-miRNA processing and stability through association with the DROSHA-processing complex during genotoxic stress.
  • APE1's endonuclease activity is essential for processing miR-221/222, which regulates the tumor suppressor PTEN.
  • APE1 participates in RNA and protein interactomes relevant to cancer development, suggesting post-transcriptional regulation of cancer genes.
  • Findings are supported by analysis of diverse cancer types.

Conclusions:

  • APE1 plays a significant role in RNA metabolism, specifically in microRNA processing.
  • APE1's function in microRNA processing impacts tumor biology by regulating genes like PTEN.
  • APE1 represents a potential therapeutic target for modulating cancer gene expression through post-transcriptional mechanisms.

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