MiR-193b, downregulated in Ewing Sarcoma, targets the ErbB4 oncogene to inhibit anchorage-independent growth

Colin Moore1, Janet K Parrish2, Paul Jedlicka2

  • 1Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, Colorado, United States of America.

Plos One
|May 26, 2017
PubMed

Insights

Researchers identified microRNA-193b (miR-193b) as a growth-suppressive factor in Ewing sarcoma. This microRNA targets the ErbB4 oncogene, offering a potential new therapeutic strategy for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ewing sarcoma is an aggressive cancer driven by oncofusions, primarily affecting young individuals.
  • Previous research identified microRNAs regulated by the EWS/Fli1 oncofusion with growth-modulatory roles.
  • Novel therapeutic targets are needed for Ewing sarcoma treatment.

Purpose of the Study:

  • To identify microRNAs repressed by EWS/Fli1 that suppress Ewing sarcoma cell growth.
  • To evaluate the therapeutic potential of replacing these microRNAs in cancer cells.

Main Methods:

  • Eight candidate microRNAs, including miR-193b, were selected based on EWS/Fli1 repression and growth-suppressive roles in other cancers.
  • MicroRNAs were introduced into Ewing sarcoma cell lines (A673, SK-ES-1) to assess growth inhibition.
  • Gene expression analysis was performed to identify miR-193b targets, focusing on ErbB4.

Main Results:

  • miR-193b significantly inhibited proliferation in both high and low-density growth assays across two Ewing sarcoma cell lines.
  • Overexpression of miR-193b suppressed anchorage-independent growth.
  • miR-193b was found to negatively regulate ErbB4 oncogene expression, and ErbB4 depletion also inhibited anchorage-independent growth.

Conclusions:

  • The EWS/Fli1-repressed miR-193b acts as a tumor suppressor in Ewing sarcoma.
  • ErbB4 is identified as a direct target of miR-193b and a potential mediator of its growth-suppressive effects.
  • miR-193b represents a promising candidate for novel therapeutic strategies against Ewing sarcoma.

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