The molecular mechanisms of SARS-CoV-2 and its potential role in cancer development
| Molecular mechanism | Description | Potential impact on cancer | Reference |
|---|---|---|---|
| Spike (S) protein and ACE2 interaction | The spike protein binds ACE2, facilitating viral entry. | ACE2 downregulation disrupts RAAS, promoting inflammation, fibrosis, and cancer progression. | [79, 80] |
| CircRNAs and miRNA interaction | SARS-CoV-2 circRNAs interact with host miRNAs. | Alters metabolic and tumorigenic pathways, potentially affecting cancer-related processes. | [81–84] |
| Dysregulation of renin-angiotensin-aldosterone system (RAAS) | ACE2 downregulation disrupts Ang-2/AT1R signaling. | Enhances inflammation, cancer stem cell formation, and oncogenic pathways (e.g., MAPK/ERK, TGF-β, IL-6, IL-8), driving tumor growth and metastasis, particularly in NSCLC. | [85–88] |
| Tumor suppressor degradation (pRB, p53) | Viral proteins (e.g., nsp15, nsp3) degrade pRB and p53. | Loss of tumor suppressors leads to uncontrolled cell proliferation and increased cancer risk. | [89–92] |
| Epigenetic modifications | SARS-CoV-2 proteins interact with epigenetic regulators (e.g., nsp7, nsp8, nsp14, SIRT5, and NSD2). | Alters gene expression; NSD2 activates RAS signaling, while SIRT5/HDAC2 modulate p53 and tumor progression. | [93–96] |
| Cytokine storm and inflammatory pathways | Severe COVID-19 triggers elevated IL-6 and other cytokines. | STAT3/NF-κB activation promotes proto-oncogene expression (e.g., c-myc), fueling tumor growth and metastasis. | [88, 97–100] |
| Viral-host protein interactions | SARS-CoV-2 proteins modulate host pathways. | Potential activation of oncogenic Wnt and NF-κB signaling, suggesting therapeutic targets. | [36, 98, 101, 102] |
ACE2: angiotensin-converting enzyme 2; Ang-2: angiopoietin-2; circRNAs: circular RNAs; COVID-19: coronavirus disease 2019; miRNA: microRNA; NSCLC: non-small cell lung cancer; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; pRB: protein retinoblastoma
