Over-expression of Bcl2-associated athanogene 2 in oral cancer promotes cellular proliferation and is associated with poor prognosis

Arch Oral Biol. 2019 Jun:102:164-170. doi: 10.1016/j.archoralbio.2019.04.015. Epub 2019 Apr 29.

Abstract

Objective: The aim of the present study was to state the role of BAG2 in oral squamous cell carcinomas (OSCC).

Design: Expression data of BAG2 in OSCC tissues were extracted from Oncomine and TCGA database. Expression levels of BAG2 mRNA and protein were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot assay. The Kaplan-Meier method was conducted to evaluate the overall survival of OSCC patients. Small interfering RNAs (siRNAs) strategy was used to confirm the effect of BAG2 expression on proliferative, invasive, migrated capacities of OSCC cells by Cell Counting kit-8 (CCK-8), colon formation assay, wound healing and transwell assay.

Results: Our results showed that BAG2 expression was up-regulated in oral squamous cell carcinomas tissues. Compared with OSCC patients with low BAG2 expression, poorer overall survival rate was found in OSCC patients with high BAG2 expression. Furthermore, proliferation, invasion and migration of HO-1-N-1 cells were significantly inhibited because of the knockdown of BAG2. Transfection of si-BAG2 has no impacts on proliferation in HNOEC cells. Inhibition of BAG2 downregulated the expression of relevant proteins, such as proliferating cell nuclear antigen (PCNA), c-Myc, matrix metalloproteinase-2 (MMP-2) and Vimentin. Additionally, the expression levels of the important protein phosphorylation (p-ERK1/2 and p-MEK) in mitogen-activated protein kinase (MAPK) pathway were reduced in HO-1-N-1 cells transfected with si-BAG2.

Conclusions: High-regulated BAG2 is related to poor prognosis and could promote proliferation, invasion and migration of OSCC cells by activating the MAPK signaling pathway. Thus, BAG2 may be a potential target for OSCC therapy.

Keywords: Bcl2-associated athanogene 2; Function role; MAPK signaling pathway; Oral cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Molecular Chaperones / metabolism*
  • Mouth Neoplasms*
  • Prognosis

Substances

  • BAG2 protein, human
  • Molecular Chaperones