MiR-770 suppresses the chemo-resistance and metastasis of triple negative breast cancer via direct targeting of STMN1

Cell Death Dis. 2018 Jan 11;9(1):14. doi: 10.1038/s41419-017-0030-7.

Abstract

Chemo-resistance and metastasis of triple negative breast cancer (TNBC) contributed the most of treatment failure in the clinic. MicroRNAs (miRNAs) have been proved to be involved in many biological processes and diseases. In this study, we aimed to determine the role of miR-770 in the regulation of chemo-resistance and metastasis of TNBC. Clinically, miR-770 was highly expressed in chemo-sensitive tissues and predicted a better prognosis of TNBC. Functionally, ectopic expression of miR-770 suppressed the doxorubicin-resistance of TNBC cell lines via regulation of apoptosis and tumor microenvironment, which was mediated by exosomes. Moreover, miR-770 overexpression inhibited the migration and invasion. Rescue of STMN1 could partly reverse the effect of miR-770 in TNBC behaviors. Furthermore, we also demonstrated that overexpression of miR-770 inhibited DOX resistance and metastasis in vivo. Taken together, our results proved that miR-770 could suppress the doxorubicin-resistance and metastasis of TNBC cells, which broaden our insights into the underlying mechanisms in chemo-resistance and metastasis, and provided a new prognostic marker for TNBC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antagomirs / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / therapeutic use
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Prognosis
  • Stathmin / chemistry
  • Stathmin / genetics
  • Stathmin / metabolism*
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Antibiotics, Antineoplastic
  • Biomarkers, Tumor
  • MIRN-770 microRNA, human
  • MicroRNAs
  • STMN1 protein, human
  • Stathmin
  • Doxorubicin
  • Nitric Oxide Synthase Type II