ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner

https://doi.org/10.1016/j.yexcr.2021.112752Get rights and content
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Highlights

  • ACBD3 is up-regulated in gastric cancer.

  • ACBD3 regulates cell-cycle of gastric cancer in an AKT-dependent manner.

Abstract

It has been reported that ACBD3 is closely related to the malignant process of cells, but its role in gastric cancer has not been elucidated. This study aims to investigate the expression and function of ACBD3 in human gastric cancer. The Cancer Genome Atlas (TCGA) database were selected to analyze mRNA levels of ACBD3 in gastric cancer tissues and normal gastric epithelial tissues. qPCR and Western blot were conducted to detect the expression of ACBD3 in two normal gastric epithelial cell lines and five gastric cancer cell lines which were cultured in our laboratory. To exclude differences in individual background between different patients, we further detected the expression of ACBD3 in 8 pairs of malignant/non-malignant clinical gastric tissues. Through the establishment of stable cells, in vitro cell experiments and in vivo xenotransplantation models in mice, the role of ACBD3 in the proliferation of gastric cancer cells has been further explored. AKT inhibitors were used to deeply explore the molecular regulation mechanism of ACBD3. The results showed that the elevated ACBD3 in gastric cancer tissue were positively correlated with the clinical grade and prognosis of gastric cancer. In terms of molecular function, we found that ACBD3 can enhance the production and growth of gastric cancer cells. At the same time, the activation of AKT kinase played an important role in ACBD3's promotion of G1-to-S transition. The experiments generally indicate that ACBD3 is expected to become a potential diagnostic molecule or therapeutic target for gastric cancer.

Keywords

ACBD3
Proliferation
Gastric cancer
AKT
G1-to-S

Abbreviations

ACBD3
Acyl-CoA binding domain containing 3
TCGA
The Cancer Genome Atlas
qPCR
Real-time quantitative PCR
GP73
Golgi protein 73
GSEA
Gene Set Enrichment Analysis
MTT
3-(4,5-Dimethyl-2-thia-zolyl)-2,5-diphenyl-2-H-tetrazolium bromide
NOD/SCID
Non-obese diabetic/severe combined immunodeficiency
BrdU
Bromodeoxyuridine
AKT
AKT serine/threonine kinase

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These authors contributed equally to this work.