miR-193b regulates tumorigenesis in liposarcoma cells via PDGFR, TGFβ, and Wnt signaling

Ying Z Mazzu1, Yulan Hu1, Yawei Shen1

  • 1Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Scientific Reports
|March 3, 2019
PubMed

Insights

MicroRNA-193b (miR-193b) suppresses liposarcoma growth by targeting PDGFRβ, SMAD4, and YAP1. Inhibiting these targets shows potential for new liposarcoma treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Liposarcoma is the most common soft tissue sarcoma.
  • Current molecularly targeted therapies for liposarcoma show limited efficacy due to complex tumor alterations.
  • MicroRNA-193b (miR-193b) has been identified as a tumor suppressor in liposarcoma.

Purpose of the Study:

  • To confirm the under-expression of miR-193b in liposarcoma.
  • To identify and validate direct targets of miR-193b in liposarcoma.
  • To investigate the therapeutic potential of targeting miR-193b pathways in liposarcoma.

Main Methods:

  • Confirmation of miR-193b under-expression in patient samples and cell lines.
  • STRING analysis to predict protein-protein interactions of miR-193b targets.
  • Validation of PDGFRβ, SMAD4, and YAP1 as direct miR-193b targets.
  • Assessment of the effects of inhibiting PDGFRβ, SMAD4, and YAP1 on liposarcoma cells.

Main Results:

  • miR-193b is significantly under-expressed in liposarcoma.
  • PDGFRβ, SMAD4, and YAP1 were validated as direct targets of miR-193b.
  • Inhibition of PDGFRβ reduced cell viability and increased adipogenesis.
  • SMAD4 knockdown promoted adipogenic differentiation.
  • miR-193b targeting of YAP1 indirectly inhibited Wnt/β-catenin signaling.
  • PDGFR and Wnt/β-catenin inhibitors demonstrated potent anti-liposarcoma effects.

Conclusions:

  • miR-193b acts as a tumor suppressor in liposarcoma by targeting multiple key signaling pathways.
  • Targeting PDGFRβ and Wnt/β-catenin signaling pathways holds promise for liposarcoma treatment.

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