BRCA1-associated protein inhibits glioma cell proliferation and migration and glioma stem cell self-renewal via the TGF-β/PI3K/AKT/mTOR signalling pathway.

Abstract

PURPOSE:

BRCA1-associated protein (BRAP) was first identified by its ability to bind to the nuclear localization signalling motif of BRCA1 and other proteins. Subsequently, human BRAP has been found to exert multiple functions, many of which are related to cancer development. Up till now, however, the role of BRAP in glioma development has remained obscure. Here, we report a role for BRAP in mediating the proliferation and migration of glioma cells both in vitro and in vivo.

METHODS:

The expression of BRAP in 98 glioma patient samples was determined by immunohistochemistry, after which associations between BRAP expression and patient prognosis were assessed. A short hairpin RNA (shRNA) was used to knock down BRAP and an expression vector was used to exogenously overexpress BRAP in glioma cells. The effects of BRAP expression on tumour cell behaviour in vitro and in an in vivo xenograft mouse model were examined.

RESULTS:

We found that in glioma patients BRAP expression was associated with a favourable prognosis. We also found that shRNA-mediated knockdown of BRAP facilitated the proliferation and migration of glioma cells and the self-renewal of glioma stem cells. In parallel, we found that BRAP knockdown increased tumour growth and invasion and decreased survival in an in vivo glioma xenograft mouse model. Mechanistically, we found that BRAP inhibited glioma cell proliferation and migration, as well as glioma stem cell self-renewal via the TGF-β/PI3K/AKT/mTOR signalling pathway.

CONCLUSIONS:

Together, our findings identify BRAP as a mediator of glioma cell proliferation, migration and glioma stem cell self-renewal.

• Authors: Bo Wang, Chen Cao, Xi Liu, Xin He, Hao Zhuang, Dong Wang, Budong Chen
• Journal: Cellular oncology (Dordrecht) (Cell Oncol (Dordr)) Vol. 43 Issue 2 Pg. 223-235 (Apr 2020) ISSN: 2211-3436 [Electronic] Netherlands
• PMID: 31776938 (Publication Type: Journal Article)

Chemical References

• Proteins
• Transforming Growth Factor beta
• BRAP protein, human
• Ubiquitin-Protein Ligases
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cell Self Renewal
• Female
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, metabolism, therapy)
• Humans
• Kaplan-Meier Estimate
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Neoplastic Stem Cells (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proteins (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA Interference
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Transforming Growth Factor beta (metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)
• Xenograft Model Antitumor Assays