Xiao Kun, Song Licheng, Bai Ying, Liu Pengfei, Liu Yuhong, Xie Fei, Xie Lixin
Center of Pulmonary and Critical Care Medicine, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Front Genet. 2021 Jul 19;12:653725. doi: 10.3389/fgene.2021.653725. eCollection 2021.
Angiotensin-converting enzyme 2 (ACE2) is an aminopeptidase that functions as a part of the renin-angiotensin system (RAS). The RAS pathway plays a crucial role in regulating the local blood flow within a tissue. As a consequence, the role of ACE2 in regulating vasculature properties has been widely appreciated. Additionally, ACE2 has also been reported to show anti-tumorigenic activity. However, the mechanistic basis of this function has remained largely unexplored. In the current study, using a lentivirus-based expression system in lung cancer cells (A549), we show that ACE2 overexpression reduces the viability and migratory potential of cancer cells, highlighting the robust anti-tumorigenic effects of ACE2 function. Moreover, a quantitative proteome-level comparison between ACE2 overexpressed (OE) and empty vector-controlled (NC) cells reveals a large number (227) of differentially expressed proteins (DEPs) that may have contributed to this phenomenon. Functional enrichment of these DEPs has uncovered that most of them perform binding activities and enzymatic reactions associated with metabolic pathways and various post-transcriptional gene expression regulatory mechanisms. Besides, cellular component analysis reveals that the DEPs function across a range of compartments within a cell with a relatively heterogeneous distribution. Our study, therefore, supports the previously established anti-tumorigenic effects of ACE2 overexpression in lung cancer cells. An analysis based on comprehensive, unbiased, and quantitative proteomics, we have provided a rigorous mechanistic explanation for its functions.
血管紧张素转换酶2（ACE2）是一种氨基肽酶，作为肾素-血管紧张素系统（RAS）的一部分发挥作用。RAS途径在调节组织内局部血流方面起着关键作用。因此，ACE2在调节血管特性方面的作用已得到广泛认可。此外，据报道ACE2还具有抗肿瘤活性。然而，这种功能的机制基础在很大程度上仍未被探索。在当前的研究中，我们在肺癌细胞（A549）中使用基于慢病毒的表达系统，表明ACE2过表达降低了癌细胞的活力和迁移潜力，突出了ACE2功能强大的抗肿瘤作用。此外，对ACE2过表达（OE）细胞和空载体对照（NC）细胞进行的定量蛋白质组水平比较揭示了大量（227个）差异表达蛋白（DEP），这些蛋白可能导致了这一现象。这些DEP的功能富集表明，它们中的大多数执行与代谢途径以及各种转录后基因表达调控机制相关的结合活性和酶促反应。此外，细胞成分分析表明，这些DEP在细胞内的一系列区室中发挥作用，分布相对不均一。因此，我们的研究支持了先前确立的ACE2过表达在肺癌细胞中的抗肿瘤作用。通过基于全面、无偏和定量蛋白质组学的分析，我们为其功能提供了严谨的机制解释。
