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Induction and Analysis of Epithelial to Mesenchymal Transition
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A double-negative feedback loop between DEAD-box protein DDX21 and Snail regulates epithelial-mesenchymal transition

Hao Zhang1, Yanqiu Zhang1, Chen Chen1

  • 1Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nan Jing, 210009, China.

Cancer Letters
|August 31, 2018
PubMed

Insights

DDX21 acts as a breast cancer metastasis suppressor. Its down-regulation, driven by miR-218-5p, promotes tumor invasion by increasing Snail transcription and epithelial-mesenchymal transition (EMT).

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • DDX21 (DEAD-box protein) is involved in RNA metabolism and its expression is altered in cancer.
  • The role of DDX21 in tumor invasion and metastasis is not fully understood.
  • Epithelial-mesenchymal transition (EMT) is a key process in cancer metastasis.

Purpose of the Study:

  • To investigate the role of DDX21 in breast cancer metastasis.
  • To elucidate the regulatory mechanisms of DDX21 and its relationship with EMT.
  • To identify potential therapeutic targets for breast cancer metastasis.

Main Methods:

  • Analysis of DDX21 expression in human breast cancer tissues.
  • In vitro and in vivo studies of DDX21 overexpression and knockdown on EMT and cell invasion.
  • Chromatin immunoprecipitation (ChIP) to assess PRC2 recruitment to the Snail promoter.
  • MicroRNA (miRNA) analysis to identify regulators of DDX21.
  • Investigation of the feedback loop between DDX21 and Snail.

Main Results:

  • DDX21 down-regulation correlates with high metastatic breast cancer and poor prognosis.
  • DDX21 overexpression inhibits EMT and cell invasion; DDX21 knockdown promotes these processes.
  • DDX21 suppresses Snail transcription via PRC2 recruitment to the Snail promoter, independent of its helicase activity.
  • miR-218-5p down-regulates DDX21, promoting EMT.
  • A double-negative feedback loop exists between DDX21 and Snail transcription.

Conclusions:

  • DDX21 functions as a tumor suppressor in breast cancer metastasis.
  • The miR-218-5p/DDX21/Snail axis is a critical regulator of EMT and metastasis.
  • Blocking miR-218-5p may represent a therapeutic strategy to stabilize DDX21, suppress Snail, and inhibit breast cancer EMT.
Keywords:
Breast cancer metastasisDDX21EMTSnailmiRNA

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