SARS-CoV-2 N protein exerts antitumor effects in NSCLC by inducing DNA damage and augmenting chemotherapeutic sensitivity

  • Med Oncol. 2025 Jun 1;42(7):230. doi: 10.1007/s12032-025-02771-9.
Xin Wang  1 ,  Fang Cao  1 ,  Di Chen  1 ,  Yunfang Bai  1 ,  Xueting Cui  2 ,  Zhicheng Luo  1 ,  Yilin Guo  1 ,  Ruilian Tong  1 ,  Mingjun Wu  3 ,  Ai-Long Huang  1 ,  Kai-Fu Tang  4
Affiliations
  • 1. Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
  • 2. Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
  • 3. Institute of Life Science, Chongqing Medical University, No.1, Yi-Xue-Yuan Road, Yu-Zhong District, Chongqing, 400016, China.
  • 4. Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China. [email protected].
PMID: 40451965 DOI: 10.1007/s12032-025-02771-9
Abstract

Recently, we reported that the SARS-CoV-2 nucleocapsid (N) protein triggers DNA damage by inducing autophagic degradation of RNAi components (Dicer and XPO5) and splicing factors (SRSF3 and hnRNPA3). In this study, we found that the SARS-CoV-2 N protein synergizes with chemotherapeutics to induce DNA damage and activate the cGAS-STING pathway in NSCLC cells. Moreover, the SARS-CoV-2 N protein acts synergistically with chemotherapeutics to suppress the proliferation and colony formation of NSCLC cells. Finally, we demonstrated that the SARS-CoV-2 N protein enhances the antitumor effects of etoposide in xenograft tumor mouse model. These findings reveal a novel antitumor mechanism of the SARS-CoV-2 N protein, positioning it as a potential therapeutic agent for lung Cancer patients.

Keywords
COVID-19; Cancer; DNA damage; SARS-CoV-2 nucleocapsid protein; cGAS-STING.
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