Caspase recruitment domain-containing protein 11 (CARD11)被报道在多种癌症中发挥作用。本研究探讨了CARD11在胃癌中的作用和机制。首先通过RNA调控百科数据库分析了CARD11在胃癌组织中的表达以及与总体生存率的关联。通过Western blot和反转录定量PCR分析检测了胃癌细胞中CARD11的表达。在CARD11沉默后，通过细胞计数套件-8试验、5-乙炔基-2'-脱氧尿嘧啶染色和流式细胞术分析评估了细胞增殖。通过伤口愈合和Transwell试验测量细胞迁移和侵袭能力。此外，通过Western blot分析检测了上皮-间质转化相关蛋白和mTOR相关蛋白的表达水平。HumanTFDB预测了转录因子Krüppel-like factor 5 (KLF5)与CARD11的启动子结合，这一点通过双荧光酶报告基因和染色质免疫共沉淀实验证实。为了探索KLF5和CARD11之间的调控作用，对CARD11沉默的胃癌细胞进行了KLF5过表达，进行了恢复实验。结果显示，CARD11在胃癌中高表达，并且与不良预后有关。CARD11干扰抑制了胃癌细胞的增殖并引起细胞周期阻滞。此外，CARD11沉默抑制了胃癌细胞的迁移、侵袭和上皮-间质转化，伴随着E-cadherin表达上调和N-cadherin和vimentin表达下调。此外，转录因子KLF5在胃癌中正向调节CARD11的转录。KLF5过表达逆转了CARD11在胃癌细胞中表达干扰的效应，促进了它们的增殖、迁移、侵袭和上皮-间质转化。KLF5过表达还导致减少细胞周期阻滞。最后，CARD11表达干扰抑制了由KLF5激活的mTOR途径。综上所述，KLF5介导的CARD11促进了胃癌细胞的增殖、迁移和侵袭。版权：©Li et al.

Caspase recruitment domain-containing protein 11 (CARD11) has been reported as functioning in multiple types of cancers. In the present study, the role and mechanism of CARD11 in gastric cancer was investigated. First, CARD11 expression in gastric cancer tissues and the association of CARD11 with overall survival were analyzed by the encyclopedia of RNA interactomes database. CARD11 expression in gastric cancer cells was detected by western blotting and reverse transcription-quantitative PCR analyses. After CARD11 silencing, cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining and flow cytometry analysis. Wound healing and Transwell assays were used to measure the capacities of cell migration and invasion. Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related proteins and mTOR-related proteins were detected by western blot analysis. HumanTFDB predicted the binding of the transcription factor Krüppel-like factor 5 (KLF5) to the CARD11 promoter, which was confirmed by dual luciferase reporter and chromatin immunoprecipitation assays. To explore the regulatory effects between KLF5 and CARD11, KLF5 was overexpressed to perform the rescue experiments in gastric cancer cells with CARD11 silencing. Results revealed that CARD11 was highly expressed in gastric cancer and was associated with poor prognosis. CARD11 interference inhibited the proliferation of gastric cancer cells and induced cell cycle arrest. Additionally, CARD11 silencing suppressed the migration, invasion and EMT of gastric cancer cells, accompanied by upregulated E-cadherin expression and downregulated N-cadherin and vimentin expression. Moreover, the transcription factor KLF5 positively regulated the transcription of CARD11 in gastric cancer. KLF5 overexpression reversed the effects of interference of CARD11 expression in gastric cancer cells to promote their proliferation, migration, invasion and EMT. KLF5 overexpression also led to a reduction in cell cycle arrest. Finally, interference of CARD11 expression suppressed the mTOR pathway, which was activated by KLF5. In conclusion, KLF5-mediated CARD11 promoted the proliferation, migration and invasion of gastric cancer cells.Copyright: © Li et al.