Down-regulation of c9orf86 in human breast cancer cells inhibits cell proliferation, invasion and tumor growth and correlates with survival of breast cancer patients

PLoS One. 2013 Aug 14;8(8):e71764. doi: 10.1371/journal.pone.0071764. eCollection 2013.


C9orf86 which is a novel subfamily within the Ras superfamily of GTPases, is overexpressed in the majority of primary breast tumors. Few functional studies have focused on the C9orf86 protein; therefore, in this study, we explored the role of C9orf86 in breast carcinogenesis. In our study, we found that silencing of C9orf86 by siRNA in MCF-7 and SK-BR-3 cells resulted in suppressed cell proliferation as well as in vitro cell invasion capabilities. Moreover, knockdown of C9orf86 inhibited tumor growth in nude mice. Cell cycle and apoptotic assays showed that the anti-proliferative effect of C9orf86-siRNA was mediated by arresting cells in the G1 phase and promoting apoptosis. In addition, we found that patients with high levels of C9orf86 expression showed a significant trend towards worse survival compared to patients with low C9orf86 expression (P = 0.002). These results provide evidence that C9orf86 represents a novel and clinically useful biomarker for BC patients and plays an important role during the progression of BC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • ras Proteins / genetics*
  • ras Proteins / metabolism


  • RABL6 protein, human
  • ras Proteins

Grant support

This work was supported in part by the National High Technology Research and Development Program of China (863 Program) (No. 20060102A4002), and State Key Laboratory Grant (985 Project II) from Ministry of Science and Technology of P.R. China. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.