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单胺氧化酶A通过消除有氧糖酵解来抑制肺腺癌细胞增殖。

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

作者信息

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

机构信息

Department of Respiratory Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Department of Respiratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou, China.

出版信息

Front Oncol. 2021 Mar 8;11:645821. doi: 10.3389/fonc.2021.645821. eCollection 2021.

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 . 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.

摘要

肺腺癌(LUAD)占所有肺癌的约30%,是全球癌症相关死亡的原因之一。由于单胺氧化酶A(MAOA)在LUAD中的作用仍不清楚,在本研究中,我们研究了MAOA如何影响LUAD细胞增殖。对公共数据和我们自己的数据进行分析后发现,与非肿瘤组织相比,LUAD中MAOA的表达下调。此外,MAOA在肿瘤中的表达与临床病理特征相关,并且MAOA的表达是LUAD中的一个独立生物标志物。此外,MAOA的过表达通过诱导G1期阻滞抑制LUAD细胞增殖。进一步的机制研究表明,MAOA通过降低己糖激酶2(HK2)来消除LUAD细胞中的有氧糖酵解。最后,HK2的表达在LUAD中与MAOA呈负相关,并且高HK2预示着不良的临床结果。总之,我们的研究结果表明MAOA在LUAD中起肿瘤抑制作用。我们的结果表明,MAOA/HK2轴可能是LUAD治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddde/7982599/b9a8d3a41a56/fonc-11-645821-g0001.jpg

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