Monoamine Oxidase A Inhibits Lung Adenocarcinoma Cell Proliferation by Abrogating Aerobic Glycolysis.

Yumin Huang,Feng Wu,Wei Zhao,Minhua Shi,Yujian Tao,Xiaoping Ouyang

doi:10.3389/fonc.2021.645821

Abstract

Lung adenocarcinoma (LUAD) accounts for ~30% of all lung cancers and is one of the causes of cancer-related death worldwide. As the role of monoamine oxidase A (MAOA) in LUAD remains unclear, in this study, we examine how MAOA affects LUAD cell proliferation. Analyses of both public data and our data reveal that the expression of MAOA is downregulated in LUAD compared with non-tumor tissue. In addition, the expression of MAOA in tumors correlates with clinicopathologic features, and the expression of MAOA serves as an independent biomarker in LUAD. In addition, the overexpression of MAOA inhibits LUAD cell proliferation by inducing G1 arrest in vitro. Further mechanistic studies show that MAOA abrogates aerobic glycolysis in LUAD cells by decreasing hexokinase 2 (HK2). Finally, the expression of HK2 shows a negative correlation with MAOA in LUAD, and high HK2 predicts poor clinical outcome. In conclusion, our findings indicate that MAOA functions as a tumor suppressor in LUAD. Our results indicate that the MAOA/HK2 axis could be potential targets in LUAD therapy.

Highlights

Lung cancer is one of the most common cancers and the leading cause of cancer-related death globally [1]
Monoamine oxidase A (MAOA) is expressed at a low level in Lung adenocarcinoma (LUAD) compared to non-tumor tissues, and the overexpression of MAOA correlates with poor outcome for LUAD according to the samples from Gene Expression Profiling Interactive Analysis (GEPIA) [20], The Cancer Genome Atlas (TCGA), and The Genotype-Tissue Expression (GTEx)
The IHC staining showed that the MAOA expression was reduced in LUAD specimens compared with non-tumor controls (Figure 1E), which was inconsistent with the mRNA results

Summary

Introduction

Lung cancer is one of the most common cancers and the leading cause of cancer-related death globally [1]. Lung adenocarcinoma (LUAD) accounts for more than 30% of all lung cancers and for about half of all non-small cell lung cancer (NSCLC) [2, 3]. Alterations of gene expression and abnormal signal pathways affect the proliferation of lung cancer [4,5,6,7], which greatly limit the treatment options. MAOA is overexpressed in prostate tumors, and it promotes cancer cell proliferation, stemness, and tumorigenesis [9, 10]. MAOA is expressed at a low level in LUAD compared to non-tumor tissues, and the overexpression of MAOA correlates with poor outcome for LUAD according to the samples from Gene Expression Profiling Interactive Analysis (GEPIA) [20], The Cancer Genome Atlas (TCGA), and The Genotype-Tissue Expression (GTEx). The expression and role of MAOA in LUAD needs further study

Methods

Results

Conclusion