SARS-CoV-2, a highly contagious coronavirus, is responsible for the global pandemic of COVID-19 in 2019. Currently, it remains uncertain whether SARS-CoV-2 possesses oncogenic or oncolytic potential in influencing tumor progression. Therefore, it is important to evaluate the clinical and functional role of SARS-CoV-2 on tumor progression. Here, we integrated bioinformatic analysis of COVID-19 RNA-seq data from the GEO database and performed functional studies to explore the regulatory role of SARS-CoV-2 in solid tumor progression, including lung, colon, kidney and liver cancer. Our results demonstrate that infection with SARS-CoV-2 is associated with a decreased expression of genes associated with cancer proliferation and metastasis in lung tissues from patients diagnosed with COVID-19. Several cancer proliferation or metastasis related genes were frequently downregulated in SARS-CoV-2 infected intestinal organoids and human colon carcinoma cells. In vivo and in vitro studies revealed that SARS-CoV-2 nucleocapsid (N) protein inhibits colon and kidney tumor growth and metastasis through the N-terminal (NTD) and the C-terminal domain (CTD). The molecular mechanism indicates that the N protein of SARS-CoV-2 interacts with YBX1, resulting in the recruitment of PKM mRNA into stress granules mediated by G3BP1. This process ultimately destabilizes PKM expression and suppresses glycolysis. Our study reveals a new function of SARS-CoV-2 nucleocapsid protein on tumor progression.

中文翻译：

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SARS-CoV-2 核衣壳蛋白与 YBX1 的相互作用通过 PKM mRNA 不稳定表现出溶瘤特性


SARS-CoV-2 是一种具有高度传染性的冠状病毒，是 2019 年 COVID-19 全球大流行的原因。目前，仍不确定 SARS-CoV-2 在影响肿瘤进展方面是否具有致癌或溶瘤潜力。因此，评估 SARS-CoV-2 对肿瘤进展的临床和功能作用非常重要。在这里，我们整合了来自 GEO 数据库的 COVID-19 RNA-seq 数据的生物信息学分析，并进行了功能研究，以探索 SARS-CoV-2 在实体瘤进展中的调节作用，包括肺癌、结肠癌、肾癌和肝癌。我们的结果表明，SARS-CoV-2 感染与诊断为 COVID-19 的患者肺组织中与癌症增殖和转移相关的基因表达降低有关。几个癌症增殖或转移相关基因在 SARS-CoV-2 感染的肠道类器官和人结肠癌细胞中经常下调。体内和体外研究表明，SARS-CoV-2 核衣壳 （N） 蛋白通过 N 端 （NTD） 和 C 端结构域 （CTD） 抑制结肠和肾脏肿瘤的生长和转移。分子机制表明，SARS-CoV-2 的 N 蛋白与 YBX1 相互作用，导致 PKM mRNA 募集到 G3BP1 介导的应激颗粒中。这个过程最终会破坏 PKM 表达的稳定性并抑制糖酵解。我们的研究揭示了 SARS-CoV-2 核衣壳蛋白对肿瘤进展的新功能。