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

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

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. tangkaifu@cqmu.edu.cn.
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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