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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Ying Z. Mazzu, Yulan Hu, Yawei Shen, Thomas Tuschl, Samuel Singer

ABSTRACT

Liposarcoma is the most common soft tissue sarcoma. Molecularly targeted therapeutics have had limited efficacy in liposarcomas, in part because of inadequate knowledge of the complex molecular alterations in these tumors. Our recent study revealed the tumor suppressive function of miR-193b in liposarcoma. Considering the biological and clinical heterogeneity of liposarcoma, here, we confirmed the under-expression of miR-193b in additional patient liposarcoma samples and cell lines. Based on STRING analysis of protein-protein interactions among the reported putative miR-193b targets, we validated three: PDGFRβ, SMAD4, and YAP1, belonging to strongly interacting pathways (focal adhesion, TGFβ, and Hippo, respectively). We show that all three are directly targeted by miR-193b in liposarcoma. Inhibition of PDGFRβ reduces liposarcoma cell viability and increases adipogenesis. Knockdown of SMAD4 promotes adipogenic differentiation. miR-193b targeting of the Hippo signaling effector YAP1 indirectly inhibits Wnt/β-catenin signaling. Both a PDGFR inhibitor (CP-673451) and a Wnt/ β-catenin inhibitor (ICG-001) had potent inhibitory effects on liposarcoma cells, suggesting their potential application in liposarcoma treatment. In summary, we demonstrate that miR-193b controls cell growth and differentiation in liposarcoma by targeting multiple key components (PDGFRβ, SMAD4, and YAP1) in several oncogenic signaling pathways. More... »

PAGES

3197

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-39560-0

DOI

http://dx.doi.org/10.1038/s41598-019-39560-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112467101

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30824765


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