Study on the potential mechanism of AIM2 regulating fatty acid synthesis and promoting cervical cancer invasion

Cervical cancer remains one of the most prevalent malignant tumors in the female reproductive system. In recent years, its incidence has continued to rise, posing a significant threat to women’s health worldwide. This study aimed to investigate whether absent in melanoma 2 (AIM2) regulates metabolic reprogramming and epithelial-mesenchymal transition (EMT) in cervical cancer cells through the Caspase-1 signaling pathway, thereby providing a potential theoretical basis for targeted therapeutic strategies. Spatial transcriptome analysis and immunohistochemistry were used to assess AIM2 expression in clinical tissues and cell lines. Stable knockdown of AIM2 was achieved in cervical cancer cell lines (SiHa and MS751) using lentivirus-mediated shRNA. Functional assays were conducted to measure cell migration and invasion. The expression levels of EMT markers (E-cadherin, N-cadherin) and key fatty acid synthesis enzymes (ACC, FASN) were analyzed through mRNA and protein detection. The role of Caspase-1 was investigated using its agonist. An in vivo mouse footpad lymph node metastasis model was utilized to validate the findings. Our study demonstrates that AIM2 is highly expressed in cervical cancer. Mechanistically, our data suggests that AIM2 may facilitate lipid accumulation and EMT progression, through the activation of the Caspase-1 signaling pathway, which is associated with the subsequent upregulation of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). This regulatory axis appears to contribute to the enhanced migratory and invasive phenotypes of cervical cancer cells. Although these findings support a putative role for the AIM2–Caspase-1 axis in tumor progression, we acknowledge that the causal pathway remains preliminary and requires further loss-of-function validation. Nevertheless, targeting this axis may represent a promising auxiliary strategy for managing cervical cancer metastasis.