肝细胞癌（HCC）对全球健康构成重大挑战。其病理生理学涉及相互关联的过程，包括细胞增殖、自噬和巨噬细胞极化。然而，黑色素瘤 2 缺席 (AIM2) 在 HCC 中的作用仍然难以捉摸。 Huh-7 和 Hep3B 细胞系中 AIM2 的表达受到操纵，细胞增殖、自噬、凋亡和迁移/侵袭，以及 M2 的极化巨噬细胞，进行了评估。通过Western blot分析检测自噬途径的标志物LC3B、Beclin-1和P62。自噬抑制剂 3-MA 用于测量自噬在 HCC 中的作用。最后，利用裸鼠皮下肿瘤模型进一步评估AIM2过表达对HCC的影响。我们的结果表明，AIM2过表达抑制HCC细胞的增殖、迁移和侵袭，同时促进细胞凋亡和自噬。相反，AIM2 的敲低会产生相反的效果。 AIM2 过表达与 M2 巨噬细胞极化减少相关。自噬抑制剂证实了 AIM2 在自噬中的作用，并确定了其对细胞增殖、迁移、侵袭和巨噬细胞极化的下游影响。在体内模型中，AIM2 的过度表达导致 HCC 肿瘤生长受到抑制。这些发现强调了 AIM2 在调节 HCC 主要生物过程中的关键功能，表明其作为治疗靶点的潜力。这项研究首次证明 AIM2 激活自噬并影响巨噬细胞极化，在肝癌进展中发挥作用。© 2024 作者。约翰·威利出版的《免疫、炎症和疾病》

Hepatocellular carcinoma (HCC) poses a significant challenge to global health. Its pathophysiology involves interconnected processes, including cell proliferation, autophagy, and macrophage polarization. However, the role of Absent in Melanoma 2 (AIM2) in HCC remains elusive.The expression of AIM2 in Huh-7 and Hep3B cell lines was manipulated and cell proliferation, autophagy, apoptosis, and migration/invasion, together with the polarization of M2 macrophages, were evaluated. The markers of autophagy pathway, LC3B, Beclin-1, and P62, underwent examination through Western blot analysis. An autophagy inhibitor, 3-MA, was used to measured the role of autophagy in HCC. Finally, the effect of AIM2 overexpression on HCC was further evaluated using a subcutaneous tumor model in nude mice.Our results established that AIM2 overexpression inhibits HCC cell proliferation, migration, and invasion while promoting apoptosis and autophagy. Conversely, knockdown of AIM2 engendered opposite effects. AIM2 overexpression was correlated with reduced M2 macrophage polarization. The autophagy inhibitor substantiated AIM2's role in autophagy and identified its downstream impact on cell proliferation, migration, invasion, and macrophage polarization. In the in vivo model, overexpression of AIM2 led to the inhibition of HCC tumor growth.The findings underscore AIM2's crucial function in modulating major biological processes in HCC, pointing to its potential as a therapeutic target. This study inaugurally demonstrated that AIM2 activates autophagy and influences macrophage polarization, playing a role in liver cancer progression.© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.