MicroRNA-409-5p is upregulated in breast cancer and its downregulation inhibits cancer development through downstream target of RSU1

Tumour Biol. 2017 May;39(5):1010428317701647. doi: 10.1177/1010428317701647.

Abstract

We investigated the expression and function of miR-409-5p in human breast cancer. Quantitative real-time polymerase chain reaction was conducted to evaluate endogenous miR-409-5p expression in breast cancer tumors and breast cancer cell lines. Lentiviral transduction was performed to stably downregulate miR-409-5p in breast cancer cell lines MDA-MB-231 and MCF-7 and cells. The effects of miR-409-5p downregulation on breast cancer proliferation, migration, and xenograft development were then evaluated. Downstream target gene of miR-409-5p, Ras suppressor protein 1, was examined by dual-luciferase activity assay, quantitative real-time polymerase chain reaction, and western blot in lentiviral-transduced breast cancer cells. Ras suppressor protein 1 was also inhibited in miR-409-5p-downregulated breast cancer cells to examine its functional effect on breast cancer proliferation and migration. MiR-409-5p was aberrantly upregulated in both breast cancer tumors and cell lines. Lentiviral transduction successfully downregulated endogenous miR-409-5p expression as well as suppressed proliferation, migration, and xenograft development in MDA-MB-231 and MCF-7 cells. Ras suppressor protein 1 was confirmed to be directly targeted by miR-409-5p in breast cancer cells. Small interfering RNA-mediated Ras suppressor protein 1 inhibition reversely promoted cancer proliferation and migration in miR-409-5p-downregualted breast cancer cells. MiR-409-5p is downregulated in breast cancer and its inhibition has anti-cancer effect on breast cancer development both in vitro and in vivo. The regulatory effect of miR-409-5p inhibition is likely through the inverse upregulation of Ras suppressor protein 1 in breast cancer.

Keywords: Breast cancer; Ras suppressor protein 1; biochemistry; cancer migration; cancer proliferation; miR-409-5p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Mice
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • RNA, Small Interfering
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcriptional Activation
  • Xenograft Model Antitumor Assays

Substances

  • MIRN409 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Transcription Factors
  • RSU1 protein, human