miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

Biochem Biophys Res Commun. 2016 Aug 5;476(4):607-613. doi: 10.1016/j.bbrc.2016.06.006. Epub 2016 Jun 3.

Abstract

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.

Keywords: Breast cancer; GRB2; Metastasis; Proliferation; miR-411-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Female
  • GRB2 Adaptor Protein / genetics*
  • GRB2 Adaptor Protein / metabolism
  • Gene Expression
  • Gene Silencing
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Signal Transduction / genetics
  • ras Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • MIRN411 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Neoplasm
  • ras Proteins