幽门螺杆菌（H.pylori）感染影响宿主细胞的细胞存活途径，包括凋亡和增殖，并且这种平衡的破坏是幽门螺杆菌引发胃癌的关键事件。幽门螺杆菌感染导致微小RNA表达异常，可能参与胃癌发展。生物信息学分析显示，在幽门螺杆菌引发的胃癌中，微小RNA-21（miR-21）显著上调。此外，我们采用定量蛋白质组学和基于计算机预测的方法，鉴定miR-21的潜在靶点。经过功能富集和集群相互作用网络分析，我们发现miR-21的5个候选靶点，即PDCD4、ASPP2、DAXX、PIK3R1和MAP3K1，涉及细胞死亡和存活、细胞运动以及细胞生长和增殖的三个功能类别。幽门螺杆菌引发的miR-21过度表达抑制了ASPP2。此外，在幽门螺杆菌引发的胃癌组织中，ASPP2水平与miR-21水平呈负相关。因此，我们将ASPP2确定为幽门螺杆菌引发的胃癌中miR-21的靶点。在这里，我们观察到幽门螺杆菌引发的ASPP2抑制增强了胃癌细胞对凋亡的抵抗力，这是通过凋亡实验获得的。通过蛋白质相互作用网络和共免疫沉淀实验证明，ATF4是幽门螺杆菌感染的胃癌细胞中ASPP2促凋亡活性的直接介导因子。在机制上，ASPP2抑制促进了p300介导的ATF4降解，从而抑制了ATF4介导的Noxa、Bak的转录和Bcl-2的抑制，进而在幽门螺杆菌感染后在胃癌细胞中实施抗凋亡。临床病理分析显示，ASPP2表达降低与高幽门螺杆菌引发的胃癌风险和不良预后相关。总之，我们发现了miR-21介导的ASPP2/ATF4信号通路抑制幽门螺杆菌引发的抗凋亡作用，为幽门螺杆菌引发的胃癌管理和治疗提供了新的视角。版权所有 © 2023年黄伯石等人。

Helicobacter pylori (H. pylori) infection affects cell survival pathways, including apoptosis and proliferation in host cells, and disruption of this balance is the key event in the development of H. pylori-induced gastric cancer (HPGC). H. pylori infection induces alterations in microRNAs expression that may be involved in GC development. Bioinformatic analysis showed that microRNA-21 (miR-21) is significantly upregulated in HPGC. Furthermore, quantitative proteomics and in silico prediction were employed to identify potential targets of miR-21. Following functional enrichment and clustered interaction network analyses, five candidates of miR-21 targets, PDCD4, ASPP2, DAXX, PIK3R1, and MAP3K1, were found across three functional clusters in association with cell death and survival, cellular movement, and cellular growth and proliferation. ASPP2 is inhibited by H. pylori-induced miR-21 overexpression. Moreover, ASPP2 levels are inversely correlated with miR-21 levels in HPGC tumor tissues. Thus, ASPP2 was identified as a miR-21 target in HPGC. Here, we observed that H. pylori-induced ASPP2 suppression enhances resistance to apoptosis in GC cells using apoptosis assays. Using protein interaction network and coimmunoprecipitation assay, we identified CHOP as a direct mediator of the ASPP2 proapoptotic activity in H. pylori-infected GC cells. Mechanistically, ASPP2 suppression promotes p300-mediated CHOP degradation, in turn inhibiting CHOP-mediated transcription of Noxa, Bak, and suppression of Bcl-2 to enact antiapoptosis in the GC cells after H. pylori infection. Clinicopathological analysis revealed correlations between decreased ASPP2 expression and higher HPGC risk and poor prognosis. In summary, the discovery of H. pylori-induced antiapoptosis via miR-21-mediated suppression of ASPP2/CHOP-mediated signaling provides a novel perspective for developing HPGC management and treatment.Copyright © 2023 Bo-Shih Huang et al.