Abstract: Objective: To investigate the expression of AIM2 in cutaneous squamous cell carcinoma (cSCC) and its correlation with ferroptosis-related indicators. Methods: Single-center samples of 25 cases of cutaneous squamous cell carcinoma tissue and corresponding adjacent tissues were selected. AIM2 expression was detected by immunohistochemistry (IHC). The effect of AIM2 on the proliferation of A431 squamous cell carcinoma cell line was assessed using the CCK-8 assay. Western blot and qPCR were employed to measure the expression levels of the ferroptosis-related redox regulatory factor HMOX1, as well as related indicators such as the antioxidant metabolite GSH and MDA. Concurrently, transmission electron microscopy was used to observe the morphological changes associated with ferroptosis in cells. Results: AIM2 was upregulated in cSCC and highly overlapped with regions of high Ki-67 expression. Knockdown of AIM2 inhibited the proliferation of A431 cells, upregulated HMOX1 expression, increased MDA levels, decreased GSH levels, and induced ferroptosisassociated morphological changes including mitochondrial atrophy and reduced cristae. Conclusion: AIM2 is highly expressed in cSCC and promotes tumor cell proliferation and disease progression by suppressing HMOX1 expression and reducing ferroptosisrelated lipid peroxidation.

Key words: AIM2, cutaneous squamous cell carcinoma, HMOX1, ferroptosis