4.5 Article

Silencing Pre-B-cell leukemia homeobox 3 decreases the proliferation of human glioma cells in vitro and in vivo

Journal

JOURNAL OF NEURO-ONCOLOGY
Volume 135, Issue 3, Pages 453-463

Publisher

SPRINGER
DOI: 10.1007/s11060-017-2603-9

Keywords

Gliomas; PBX3; Proliferation; Apoptosis; Cell cycle

Funding

  1. National Natural Science Foundation of China [81300998, 81471269]
  2. National Natural Science Foundation of Jiangsu Province [BK20131022, BK20160047]
  3. Jiangsu Province's Key Discipline of Medicine [XK201117]
  4. Jiangsu Province
  5. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
  6. Specially-Appointed Professor Foundation of Jiangsu Province [ky216r201307]

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Among primary brain tumors, gliomas are the most common and most aggressive, with a poor prognosis and limited treatment options. Thus, it is essential to determine the mechanisms involved in glioma development to develop effective therapies for glioma patients. Pre-B-cell leukemia homeobox 3 (PBX3), a critical member of the PBX family, is frequently overexpressed in multiple human malignancies. However, the expression patterns and biological functions, as well as the involved molecular functions of PBX3 in human gliomas remain largely unknown. In this study, we demonstrate that PBX3 expression is increased in both human glioma tissues and cell lines compared with their normal counterparts. These results suggested that PBX3 might be involved in glioma progression. Thus, the role of PBX3 in glioma cell proliferation was investigated using genetic knockdown and overexpression methods. The results showed that PBX3 knockdown inhibited glioma cell proliferation and induced apoptosis, while PBX3 overexpression significantly promoted glioma cell proliferation. Mechanistically, we found that PBX3 promoted cell proliferation by modulating cell cycle progression. A xenograft LN229 model was used to confirm that PBX3 depletion decreased tumor growth in vivo. In summary, our findings reveal that PBX3 may be a potential therapeutic target in gliomas.

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