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Dual mechanism of DICER downregulation facilitates cancer metastasis

Hui-Huang Lai1,2, Pai-Sheng Chen1,2

  • 1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.

Molecular & Cellular Oncology
|September 29, 2018
PubMed

Insights

Hypoxia-inducible factor-1α (HIF-1α) promotes cancer metastasis by directly binding to DICER, suppressing microRNA (miRNA) production through a novel autophagic pathway. This discovery reveals a new mechanism driving cancer spread.

Area of Science:

  • Molecular oncology
  • Cancer biology
  • Cellular mechanisms

Background:

  • Downregulation of DICER, crucial for microRNA (miRNA) maturation, is linked to cancer metastasis.
  • The upstream regulators of DICER and their role in metastasis are not fully understood.

Purpose of the Study:

  • To investigate the noncanonical oncogenic role of hypoxia-inducible factor-1α (HIF-1α) in cancer metastasis.
  • To elucidate the molecular mechanism by which HIF-1α influences DICER and miRNA biogenesis.

Main Methods:

  • Investigated the direct interaction between HIF-1α and DICER.
  • Assessed the role of PARKIN-mediated autophagic-lysosomal proteolysis in DICER degradation.
  • Quantified the impact on miRNA biogenesis and cancer cell metastasis.

Main Results:

  • HIF-1α directly binds to DICER, promoting its degradation via PARKIN-mediated autophagic-lysosomal proteolysis.
  • This interaction leads to suppressed miRNA biogenesis.
  • The suppression of miRNA biogenesis by HIF-1α facilitates cancer metastasis.

Conclusions:

  • HIF-1α exerts a noncanonical oncogenic effect by targeting DICER for degradation.
  • This pathway represents a novel mechanism contributing to cancer metastasis through miRNA suppression.
  • Targeting the HIF-1α-DICER interaction may offer new therapeutic strategies for metastatic cancers.
Keywords:
DICERHIF-1αmetastasismiRNA

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