Suppression of SOX18 by siRNA inhibits cell growth and invasion of breast cancer cells

Oncol Rep. 2016 Jun;35(6):3721-7. doi: 10.3892/or.2016.4746. Epub 2016 Apr 15.

Abstract

Breast cancer is the most common malignancy in women around the world, and its incidence and mortality rates are still rising. An increasing number of studies have reported that SOX18 plays an important role in various cancers. However, the role of SOX18 in breast cancer remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of SOX18 in breast cancer. We found that the mRNA and protein expression levels of SOX18 were prevalently and significantly overexpressed in human breast cancer cell lines. Next, we performed loss-of-function experiments by transfection of two breast cancer cell lines, BT-474 and MCF-7, with SOX18 small interfering RNAs (siRNA). Results showed that SOX18 siRNA transfection significantly suppressed mRNA and protein expression of SOX18 in breast cancer cells. Furthermore, knockdown of SOX18 significantly inhibited cell proliferation and invasion, but promoted apoptosis in breast cancer cells. Importantly, several oncogenic proteins, including the Ras homolog gene family member A (RhoA), platelet-derived growth factor B (PDGFB), Insulin-like growth factor 1 receptor (IGF-1R), and matrix metalloproteinase-7 (MMP-7), were markedly decreased by SOX18 siRNA. Taken together, the results of our study suggest that knockdown of SOX18 inhibits breast cancer cell growth and invasion, possibly by downregulating downstream oncogenic proteins, providing novel insights into the development of breast cancer therapy through targeting of SOX18.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Female
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 7 / metabolism*
  • Neoplasm Invasiveness / genetics
  • Proto-Oncogene Proteins c-sis / metabolism*
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOXF Transcription Factors / genetics*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • RNA, Small Interfering
  • SOX18 protein, human
  • SOXF Transcription Factors
  • RHOA protein, human
  • Receptor, IGF Type 1
  • Caspase 3
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • rhoA GTP-Binding Protein