Deep sequencing reveals a novel miR-22 regulatory network with therapeutic potential in rhabdomyosarcoma Academic Article uri icon


MeSH Major

  • Gene Regulatory Networks
  • High-Throughput Nucleotide Sequencing
  • MicroRNAs
  • Rhabdomyosarcoma


  • Current therapeutic options for the pediatric cancer rhabdomyosarcoma have not improved significantly, especially for metastatic rhabdomyosarcoma. In the current work, we performed a deep miRNA profiling of the three major human rhabdomyosarcoma subtypes, along with cell lines and normal muscle, to identify novel molecular circuits with therapeutic potential. The signature we determined could discriminate rhabdomyosarcoma from muscle, revealing a subset of muscle-enriched miRNA (myomiR), including miR-22, which was strongly underexpressed in tumors. miR-22 was physiologically induced during normal myogenic differentiation and was transcriptionally regulated by MyoD, confirming its identity as a myomiR. Once introduced into rhabdomyosarcoma cells, miR-22 decreased cell proliferation, anchorage-independent growth, invasiveness, and promoted apoptosis. Moreover, restoring miR-22 expression blocked tumor growth and prevented tumor dissemination in vivo Gene expression profiling analysis of miR-22-expressing cells suggested TACC1 and RAB5B as possible direct miR-22 targets. Accordingly, loss- and gain-of-function experiments defined the biological relevance of these genes in rhabdomyosarcoma pathogenesis. Finally, we demonstrated the ability of miR-22 to intercept and overcome the intrinsic resistance to MEK inhibition based on ERBB3 upregulation. Overall, our results identified a novel miR-22 regulatory network with critical therapeutic implications in rhabdomyosarcoma. Cancer Res; 76(20); 6095-106. ©2016 AACR.

publication date

  • October 15, 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC5207039

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-16-0709

PubMed ID

  • 27569217

Additional Document Info

start page

  • 6095

end page

  • 6106


  • 76


  • 20