Abstract
BackgroundAcylphosphatase 2 (ACYP2) is involved in cell differentiation, energy metabolism and hydrolysis of intracellular ion pump. It has been reported as a negative regulator in leukemia and a positive regulator in colon cancer, respectively. However, its biological role in glioma remains totally unclear.MethodsWe performed quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC) and western blot assays to evaluate ACYP2 expression. The functions of ACYP2 in glioma cells were determined by a series of in vitro and in vivo experiments, including cell proliferation, colony formation, cell cycle, apoptosis, migration, invasion and nude mouse tumorigenicity assays. In addition, western blot and co-immunoprecipitation (Co-IP) assays were used to identify its downstream targets.ResultsKnocking down ACYP2 in glioma cells significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Conversely, ectopic expression of ACYP2 in glioma cells dramatically promoted malignant phenotypes of glioma cells. Mechanistically, ACYP2 promoted malignant progression of glioma cells through regulating intracellular Ca2+ homeostasis via its interaction with PMCA4, thereby activating c-Myc and PTP1B/STAT3 signals. This could be effectively reversed by Ca2+ chelator BAPTA-AM or calpain inhibitor calpeptin.ConclusionsOur data demonstrate that ACYP2 functions as an oncogene in glioma through activating c-Myc and STAT3 signals via the regulation of intracellular Ca2+ homeostasis, and indicate that ACYP2 may be a potential therapeutic target and prognostic biomarker in gliomas.
Highlights
Acylphosphatase 2 (ACYP2) is involved in cell differentiation, energy metabolism and hydrolysis of intracellular ion pump
Increased expression of ACYP2 is associated with poor survival in low-grade glioma (LGG) patients We first examined mRNA and protein expression of ACYP2 in 52 gliomas and 24 normal brain tissues by quantitative RT-PCR (qRT-PCR), immunohistochemistry and western blot assays
Through analyzing the Cancer Genome Atlas (TCGA) dataset, we found that increased expression of ACYP2 was clearly associated with poor survival in low-grade glioma (LGG) patients
Summary
Acylphosphatase 2 (ACYP2) is involved in cell differentiation, energy metabolism and hydrolysis of intracellular ion pump. It has been reported as a negative regulator in leukemia and a positive regulator in colon cancer, respectively. Gliomas are the most common malignant tumor in the central nervous system, and the overall estimated annual incidence for gliomas ranges from 4.67 to 5.73 per 100,000 individuals [1,2,3] They originate from brain interstitial cells and hold the characteristics of diffuse infiltrative growth, no definite boundaries and highly invasive. The above observations indicate that ACYP may be involved in tumor initiation and progression; there are no studies available to determine their role in gliomas
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