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Published on: April 3, 2018
SARS-CoV-2 nucleocapsid protein interaction with YBX1 displays oncolytic properties through PKM mRNA destabilization
Xin Chen1, Baohong Jiang2, Yu Gu1
1Institute of Medical Microbiology, Key Laboratory of Viral Pathogenesis & Infection Prevention and Control, Jinan University, Ministry of Education, Guangzhou, 510632, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
Our study reveals a new function of SARS-CoV-2 nucleocapsid protein on tumor progression.
Insights
The SARS-CoV-2 nucleocapsid protein inhibits tumor growth and metastasis by downregulating cancer-related genes. This discovery reveals a novel oncolytic function for the virus, impacting cancer progression.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19.
- The oncogenic or oncolytic potential of SARS-CoV-2 in tumor progression remains unclear.
- Evaluating the role of SARS-CoV-2 in cancer is crucial.
Purpose of the Study:
- To investigate the regulatory role of SARS-CoV-2 in solid tumor progression.
- To explore the impact of SARS-CoV-2 infection on cancer-related genes.
- To elucidate the molecular mechanisms by which SARS-CoV-2 influences tumor growth and metastasis.
Main Methods:
- Bioinformatic analysis of COVID-19 RNA-seq data from the GEO database.
- Functional studies in lung, colon, kidney, and liver cancer models.
- In vivo and in vitro experiments using SARS-CoV-2 nucleocapsid (N) protein.
Main Results:
- SARS-CoV-2 infection decreased cancer proliferation and metastasis genes in lung tissues.
- SARS-CoV-2 nucleocapsid (N) protein inhibited colon and kidney tumor growth and metastasis.
- N protein interacts with YBX1, leading to PKM mRNA destabilization and suppressed glycolysis.
Conclusions:
- SARS-CoV-2 nucleocapsid protein exhibits a novel oncolytic function.
- The N protein suppresses tumor progression by inhibiting glycolysis.
- This study uncovers a new role for SARS-CoV-2 in cancer biology.
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