MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

Abstract

Objective: Previous studies have indicated that neurotransmitters play important roles in the occurrence and development of gastric cancer. MAOA is an important catecholamine neurotransmitter-degrading enzyme involved in the degradation of norepinephrine, epinephrine and serotonin. To find a potential therapeutic target for the treatment of gastric cancer, the biological functions of MAOA and the underlying mechanism in gastric cancer need to be explored.

Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets, Kaplan‒Meier (KM) plotter were used to identify the differentially expressed genes, which mainly involved the degradation and synthesis enzymes of neurotransmitters in gastric cancer. We also investigated the expression pattern of MAOA in human and mouse tissues and cell lines by immunohistochemistry and Western blotting analysis. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and a Seahorse experiment were used to identify the molecular mechanism of cancer cell glycolysis. MAOA expression and patient survival were analysed in the Ren Ji cohort, and univariate and multivariate analyses were performed based on the clinicopathological characteristics of the above samples.

Results: MAOA expression was significantly downregulated in gastric cancer tissue and associated with poor patient prognosis. Moreover, the expression level of MAOA in gastric cancer tissue had a close negative correlation with the SUXmax value of PET-CT in patients. MAOA suppressed tumour growth and glycolysis and promoted cancer cell apoptosis. We also reported that MAOA can interact with NDRG1 and regulate glycolysis through suppression of the PI3K/Akt/mTOR pathway. MAOA expression may serve as an independent prognostic factor in gastric cancer patients.

Conclusions: MAOA attenuated glycolysis and inhibited the progression of gastric cancer through the PI3K/Akt/mTOR pathway. Loss of function or downregulation of MAOA can facilitate gastric cancer progression. Overexpression of MAOA and inhibition of the PI3K/Akt/mTOR pathway may provide a potential method for gastric cancer treatment in clinical therapeutic regimens.

Keywords: Gastric cancer; Monoamine oxidase A; PI3K/AKT/mTOR pathway; Warburg effect.