microRNA-370 Promotes Cell Growth by Targeting WNK2 in Breast Cancer

DNA Cell Biol. 2019 Jun;38(6):501-509. doi: 10.1089/dna.2018.4602. Epub 2019 Apr 22.


Aberrant expression of microRNA-370 (miR-370) has been found in many types of human cancers. In non-small cell lung cancer, miR-370 is a tumor suppressor with decreased expression. In prostate cancer, it is an oncogene with overexpression. Although upregulation of miR-370 was correlated with poor prognosis of breast cancer, the exact function of miR-370 is largely unclear. The roles of miR-370 in breast cancer are investigated, and its downstream targets are identified. miR-370 expression was detected by reverse transcription polymerase chain reaction in breast cancer cells. Cell growth curve and colony formation were monitored on overexpressing or knocking down miR-370. We further identified the target of miR-370 and the role of the target in tumorigenesis by using western blot, luciferase assay, and the xenograft mouse model. miR-370 is increased in breast cancer cells. Its overexpression promotes cell growth, whereas the knockdown of miR-370 suppresses cell growth. WNK2 is a downstream target of miR-370. Manipulation of WNK2 expression affects miR-370-mediated cell proliferation and tumor growth. Our data suggest that miR-370 acts as an oncogene by downregulating WNK2 in breast cancer, providing a molecular basis for clinical application of miR-370 as a potential biomarker.

Keywords: WNK2; breast cancer; colony formation; miR-370; proliferation; tumor growth.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism


  • 3' Untranslated Regions
  • MIRN370 microRNA, human
  • MicroRNAs
  • WNK2 protein, human
  • Protein Serine-Threonine Kinases