Department of liver diseases, Shandong public health clinical center, Shandong university, Jinan, Shandong, China.
Immun Inflamm Dis. 2024 Sep;12(9):e70002. doi: 10.1002/iid3.70002.
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.
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，AIM2 在 HCC 中的作用仍不清楚。
操纵 Huh-7 和 Hep3B 细胞系中 AIM2 的表达，评估细胞增殖、自噬、凋亡和迁移/侵袭，以及 M2 巨噬细胞的极化。通过 Western blot 分析检测自噬途径的标志物 LC3B、Beclin-1 和 P62。使用自噬抑制剂 3-MA 测量自噬在 HCC 中的作用。最后，使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 细胞增殖、迁移和侵袭，同时促进细胞凋亡和自噬。相反，AIM2 的敲低产生了相反的效果。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 中主要生物学过程中的关键作用，表明其作为治疗靶点的潜力。这项研究首次表明，AIM2 激活自噬并影响巨噬细胞极化，在肝癌进展中发挥作用。
