Anti-miR-203 suppresses ER-positive breast cancer growth and stemness by targeting SOCS3

Oncotarget. 2016 Sep 6;7(36):58595-58605. doi: 10.18632/oncotarget.11193.

Abstract

Breast cancer is a major public health problem worldwide in women and existing treatments are not adequately effective for this deadly disease. microRNAs (miRNAs) regulate the expression of many target genes and play pivotal roles in the development, as well as in the suppression of many cancers including breast cancer. We previously observed that miR-203 was highly upregulated in breast cancer tissues and in ER-positive breast cancer cell lines. In our present study, we observed that anti-miR-203 suppresses breast cancer cell proliferation in vitro. Orthotopic implantation of miR-203 depleted MCF-7 cells into nude mice displays smaller tumor growth as compared to control MCF-7 cells. Furthermore, miR-203 expression is significantly higher in ER-positive breast cancer patients as compared to ER-negative patients. We identified suppressor of cytokine signaling 3 (SOCS3) as a direct target of miR-203. Here we observed that miR-203 expression is inversely correlated with SOCS3 expression in ER-positive breast cancer samples. Additionally, we found that anti-miR-203 suppressed the expression of pStat3, pERK and c-Myc in MCF-7 and ZR-75-1 cells. We also demonstrated that anti-miR-203 decreased mammospheres formation and expression of stem cell markers in MCF-7 and ZR-75-1 cells. Taken together, our data suggest that anti-miR-203 has potential as a novel therapeutic strategy in ER-positive breast cancer treatment.

Keywords: SOCS3; breast cancer; miR-203; stemness.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 6 / metabolism
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / cytology
  • Proto-Oncogene Proteins c-myc / metabolism
  • STAT3 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 3 Protein / metabolism*

Substances

  • ESR1 protein, human
  • Estrogen Receptor alpha
  • MIRN203 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • SOCS3 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Mitogen-Activated Protein Kinase 6