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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2

Yosuke Harazono1, Tomoki Muramatsu, Hironori Endo

  • 1Department of Molecular Cytogenetics, Tokyo Medical and Dental University, Tokyo, Japan.

Plos One
|May 22, 2013
PubMed

Insights

MicroRNA-655 (miR-655) suppresses cancer progression by inhibiting the epithelial-to-mesenchymal transition (EMT). This novel EMT-suppressive miRNA targets ZEB1 and TGFBR2, offering potential therapeutic strategies for cancers like esophageal squamous cell carcinoma.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The epithelial-to-mesenchymal transition (EMT) is implicated in normal development and disease, notably cancer progression.
  • Identifying microRNAs (miRNAs) that suppress EMT is crucial for understanding and potentially treating cancer.

Purpose of the Study:

  • To discover novel microRNAs (miRNAs) that inhibit the epithelial-to-mesenchymal transition (EMT).
  • To investigate the role of miR-655 in cancer cell migration, invasion, and prognosis.

Main Methods:

  • Established a cell-based reporter system using Panc1 pancreatic cancer cells and a CDH1/E-cadherin promoter-driven reporter construct.
  • Conducted a functional screen of 470 synthetic microRNA mimics to identify EMT-suppressive miRNAs.
  • Validated targets and assessed the impact of miR-655 overexpression on cancer cell phenotype, migration, invasion, and prognosis.

Main Results:

  • Identified miR-655 as a novel EMT-suppressive miRNA.
  • Overexpression of miR-655 upregulated E-cadherin, downregulated EMT-inducers, and suppressed cancer cell migration and invasion.
  • Found a correlation between higher miR-655 expression and better prognosis in esophageal squamous cell carcinoma (ESCC).
  • Identified ZEB1 and TGFBR2 as direct targets of miR-655, implicating the TGF-b signaling pathway.

Conclusions:

  • miR-655 acts as a tumor suppressor by inhibiting EMT, targeting key components of the TGF-b signaling pathway (ZEB1, TGFBR2).
  • Aberrant downregulation of miR-655 may accelerate cancer progression through activation of the TGF-b-ZEB1-E-cadherin axis.
  • miR-655 represents a potential therapeutic target for cancers exhibiting EMT, including esophageal squamous cell carcinoma.

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