The role of monoamine oxidase A in HPV-16 E7-induced epithelial-mesenchymal transition and HIF-1α protein accumulation in non-small cell lung cancer cells

作者：Bingyu Huang, Zhiyuan Zhou, Jiao Liu, Xin Wu, Xiangyong Li, Qiang He, Peihua Zhang, Xudong Tang · 发表于：International Journal of Biological Sciences · 年份：2020 · DOI：10.7150/ijbs.46966 · 被引用次数：38 · 研究领域：Cancer, Hypoxia, and Metabolism、Cancer, Stress, Anesthesia, and Immune Response、Metabolism, Diabetes, and Cancer

Our previous studies have found that human papillomavirus (HPV)-16 E7 oncoprotein promotes epithelial-mesenchymal transition (EMT) and hypoxia-inducible factor-1 (HIF-1) protein accumulation in non-small cell lung cancer (NSCLC) cells and monoamine oxidase A (MAOA) is highly expressed in NSCLC tissues. Here, we further explored the role of MAOA in HPV-16 E7-induced EMT and HIF-1 protein accumulation in A549 and NCI-H460 NSCLC cells. Our results showed that HPV-16 E7 enhanced MAOA expression in NSCLC cells. Additionally, MAOA knockout inhibited HPV-16 E7-induced migration, invasion, and EMT, and significantly reduced HPV-16 E7-induced ROS generation and HIF-1 protein accumulation via promoting its degradation. Furthermore, MAOA knockout suppressed HPV-16 E7-induced ERK1/2 activation. In vivo, MAOA knockout inhibited tumor growth, metastasis, and the expression of EMT-related markers and HIF-1 proteins induced by HPV-16 E7 in NCI-H460 NSCLC subcutaneous xenograft and in situ intrapulmonary models of nude mice. Taken together, our findings provide evidence that MAOA plays a key role in EMT and HIF-1 protein accumulation induced by HPV-16 E7 in NSCLC cells, suggesting that MAOA may be a potential therapeutic target for HPV-related NSCLC.