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Tumor Biology

, Volume 36, Issue 11, pp 8931–8942 | Cite as

Bmi-1 is essential for the oncogenic potential in CD133+ human laryngeal cancer cells

  • Xudong Wei
  • Jian He
  • Jingyu Wang
  • Xiaolong Yang
  • Bingjuan Ma
Research Article

Abstract

It has been hypothesized that cancer stem cells (CSCs) are a principal culprit of tumor initiation, invasion, metastasis, and treatment resistance. Previous studies have confirmed that cancer stem cells can be detected in laryngeal carcinoma. This study aimed to evaluate whether population of CD133+ cells that existed in primary human laryngeal carcinoma have characteristic of CSCs with enhanced capacity of proliferation and invasion, and to understand whether and how Bmi-1 implicated in self-renewal and tumorigenesis. We clarified the tumorigenic potential of CD133 sorted populations of cancer cells derived from primary human laryngeal tumor sample. After fluorescence activated cell sorting, real-time polymerase chain reaction (PCR) and western blot confirmed Bmi-1 was differentially expressed in CD133 sorted laryngeal tumor cells. Bmi-1 was knocked down, and proliferation, colony formation, invasion, cell cycle assay, and apoptosis assays were performed, and the impact on Bmi-1 pathway was evaluated. It was found that CD133+ cells existed in primary human laryngeal tumor with enhanced capacity of proliferation and invasion. Bmi-1, implicated in self-renewal and tumorigenesis, was coexpressed with the CD133. Furthermore, knockdown of Bmi-1 expression in CD133+ cells led to inhibition of cell growth, colony formation, cell invasion in vitro, and tumorigenesis in vivo, through up-regulation of p16INK4A and p14ARF. Our data indicate that Bmi-1 expression is central to the tumorigenicity of CD133+ cells, which functions as a pleiotropic regulator that maintains the viability and proliferative capacity of human laryngeal tumor. It negatively regulates the transcription of the downstream INK4a/ARF gene and inhibits expression of P16ink4a/P14ARF, so as to maintain the high ability of proliferation and differentiation in laryngeal cancer stem cells.

Keywords

Laryngeal carcinoma Cancer stem cells Bmi-1 gene 

Notes

Acknowledgments

The study was funded by the National Natural Science Foundation of China (no. 81060224), Technology Research and Development Plan of Gansu Province (no. 1205TCYA043), and Foundation of Lanzhou Science and Technology Development Plan (no. 2013-3-31).

Conflicts of interests

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xudong Wei
    • 1
  • Jian He
    • 1
  • Jingyu Wang
    • 2
  • Xiaolong Yang
    • 1
  • Bingjuan Ma
    • 1
  1. 1.Department of Otolaryngology–Head and Neck Surgery, Gansu ProvinceGansu Provincial HospitalLanzhouChina
  2. 2.Institute of PathophysiologyLanzhou UniversityLanzhouChina

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