Potent and selective effect of the mir-10b inhibitor MN-anti-mir10b in human cancer cells of diverse primary disease origin

PLoS One. 2018 Jul 20;13(7):e0201046. doi: 10.1371/journal.pone.0201046. eCollection 2018.

Abstract

Since microRNAs (miRNAs, miRs) have been implicated in oncogenesis, many of them have been identified as therapeutic targets. Previously we have demonstrated that miRNA-10b acts as a master regulator of the viability of metastatic tumor cells and represents a target for therapeutic intervention. We designed and synthesized an inhibitor of miR-10b, termed MN-anti-miR10b. We showed that treatment with MN-anti-miR10b led to durable regression/elimination of established metastases in murine models of metastatic breast cancer. Since miRNA-10b has been associated with various metastatic and non-metastatic cancers, in the present study, we investigated the effect of MN-anti-miR10b in a panel of over 600 cell lines derived from a variety of human malignancies. We observed an effect on the viability of multiple cell lines within each cancer type and a mostly dichotomous response with cell lines either strongly responsive to MN-anti-miR10b or not at all even at maximum dose tested, suggesting a very high specificity of the effect. Genomic modeling of the drug response showed enrichment of genes associated with the proto-oncogene, c-Jun.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antagomirs / pharmacology*
  • Antagomirs / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Female
  • Genomics
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Proto-Oncogene Mas

Substances

  • Antagomirs
  • MAS1 protein, human
  • MIRN10 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas