Our previous studies have found that human papillomavirus (HPV)-16 E7 oncoprotein promotes epithelial-mesenchymal transition (EMT) and hypoxia-inducible factor-1α (HIF-1α) 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-1α 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-1α 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-1α 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-1α protein accumulation induced by HPV-16 E7 in NSCLC cells, suggesting that MAOA may be a potential therapeutic target for HPV-related NSCLC.

中文翻译：

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单胺氧化酶A在HPV-16 E7诱导的非小细胞肺癌细胞上皮间质转化和HIF-1α蛋白积累中的作用。

我们之前的研究发现人乳头瘤病毒 (HPV)-16 E7 癌蛋白促进非小细胞肺癌 (NSCLC) 细胞和单胺中的上皮间质转化 (EMT) 和缺氧诱导因子-1α (HIF-1α) 蛋白积累氧化酶 A (MAOA) 在 NSCLC 组织中高度表达。在这里，我们进一步探讨了 MAOA 在 A549 和 NCI-H460 NSCLC 细胞中 HPV-16 E7 诱导的 EMT 和 HIF-1α 蛋白积累中的作用。我们的结果表明 HPV-16 E7 增强了 NSCLC 细胞中的 MAOA 表达。此外，MAOA 敲除抑制了 HPV-16 E7 诱导的迁移、侵袭和 EMT，并通过促进其降解显着减少了 HPV-16 E7 诱导的 ROS 生成和 HIF-1α 蛋白积累。此外，MAOA 敲除抑制了 HPV-16 E7 诱导的 ERK1/2 激活。体内在 NCI-H460 NSCLC 皮下异种移植和裸鼠原位肺内模型中，MAOA 敲除抑制了肿瘤生长、转移以及 HPV-16 E7 诱导的 EMT 相关标志物和 HIF-1α 蛋白的表达。总之，我们的研究结果提供证据表明 MAOA 在 HPV-16 E7 诱导的 NSCLC 细胞中的 EMT 和 HIF-1α 蛋白积累中起关键作用，表明 MAOA 可能是 HPV 相关 NSCLC 的潜在治疗靶点。