Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China.
Department of General Surgery, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, China.
Sci Rep. 2021 Apr 15;11(1):8235. doi: 10.1038/s41598-021-87744-4.
Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and poses a great threat to public health. Absent in melanoma 2 (AIM2), a member of the pyrin-HIN family proteins, plays various roles across different types of cancers. However, the possible role of AIM2 in GC, as well as the underling mechanisms, are equivocal and need to be further explored. Herein, we identified that AIM2 expression was significantly down-regulated in GC tissues. Furthermore, loss of AIM2 was significantly associated with tumor size, lymph node metastasis (LNM) and tumor, node, metastases (TNM) staging, as well as poor prognosis in GC patients. Knockdown of AIM2 in GC cells significantly promoted cellular proliferation and migration, whereas AIM2 overexpression did the opposite. Mechanistically, we discovered that AIM2 regulates the AKT signaling pathway. In fact, the enhanced proliferation and migration ability induced by AIM2 knockdown was partially impaired in cells treated with the AKT inhibitor. Overall, our findings suggests that AIM2 is an independent prognostic marker and highlights a new entry point for targeting the AIM2/AKT signaling axis for GC treatment.
胃癌（GC）是全球癌症相关死亡的第三大主要原因，对公众健康构成了巨大威胁。缺失在黑色素瘤 2（AIM2）中，一种吡喃-HIN 家族蛋白成员，在不同类型的癌症中发挥着各种作用。然而，AIM2 在 GC 中的可能作用以及潜在机制仍存在争议，需要进一步探索。在此，我们发现 AIM2 的表达在 GC 组织中显著下调。此外，AIM2 的缺失与肿瘤大小、淋巴结转移（LNM）和肿瘤、淋巴结、转移（TNM）分期以及 GC 患者的不良预后显著相关。在 GC 细胞中敲低 AIM2 显著促进了细胞增殖和迁移，而 AIM2 的过表达则起到了相反的作用。在机制上，我们发现 AIM2 调节 AKT 信号通路。事实上，在 AKT 抑制剂处理的细胞中，AIM2 敲低诱导的增殖和迁移能力的增强部分受损。总的来说，我们的研究结果表明，AIM2 是一个独立的预后标志物，并为针对 GC 治疗的 AIM2/AKT 信号轴提供了一个新的靶点。
