Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350122, PR China; Department of Gynecology, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, Fujian 352100, PR China.
Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350122, PR China; Department of Central Laboratory, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, Fujian 352100, PR China.
Tissue Cell. 2023 Jun;82:102083. doi: 10.1016/j.tice.2023.102083. Epub 2023 Apr 5.
To explore the effects and mechanisms of action of the PBX1/secreted frizzled-related protein 4 (SFRP4) axis in endometrial carcinoma (EC).
The expression of PBX1 and SFRP4 was analyzed using bioinformatics prediction, followed by validation in EC cells using quantitative reverse transcription-polymerase chain reaction and western blotting. After transduction with overexpression vectors for PBX1 and SFRP4, migration, proliferation, and invasion of EC cells were measured, accompanied by the detection of E-cadherin, Snail, N-cadherin, Vimentin, β-catenin, GSK-3β, and C-myc expression. The association between PBX1 and SFRP4 was validated using dual luciferase reporter gene and chromatin immunoprecipitation assays.
PBX1 and SFRP4 were downregulated in EC cells. Overexpression of PBX1 or SFRP4 resulted in weakened cell proliferation, migration, and invasion, as well as decreased expression of Snail, N-cadherin, Vimentin, β-catenin, GSK-3β, and C-myc and increased expression of E-cadherin. PBX1 bound to the SFRP4 promoter and promoted its transcription. Knockdown of SFRP4 reversed the repression of overexpressed PBX1 in the malignant phenotypes and EMT of EC cells, and PBX1 repressed Wnt/β-catenin pathway activation by upregulating SFRP4 transcription.
PBX1 inhibited activation of the Wnt/β-catenin pathway by promoting SFRP4 transcription, thereby suppressing malignant phenotypes in EC cells and the EMT process.
探讨 PBX1/分泌型卷曲相关蛋白 4（SFRP4）轴在子宫内膜癌（EC）中的作用及作用机制。
利用生物信息学预测分析 PBX1 和 SFRP4 的表达，并用定量逆转录聚合酶链反应和蛋白质印迹法在 EC 细胞中验证。转染 PBX1 和 SFRP4 的过表达载体后，检测 EC 细胞的迁移、增殖和侵袭能力，并检测 E-钙黏蛋白、Snail、N-钙黏蛋白、波形蛋白、β-连环蛋白、GSK-3β 和 C-myc 的表达。利用双荧光素酶报告基因和染色质免疫沉淀实验验证 PBX1 和 SFRP4 之间的关联。
PBX1 和 SFRP4 在 EC 细胞中表达下调。过表达 PBX1 或 SFRP4 导致细胞增殖、迁移和侵袭能力减弱，Snail、N-钙黏蛋白、波形蛋白、β-连环蛋白、GSK-3β 和 C-myc 的表达降低，E-钙黏蛋白的表达增加。 PBX1 与 SFRP4 启动子结合并促进其转录。沉默 SFRP4 可逆转过表达 PBX1 对 EC 细胞恶性表型和 EMT 的抑制作用， PBX1 通过上调 SFRP4 转录抑制 Wnt/β-连环蛋白通路的激活。
PBX1 通过促进 SFRP4 转录抑制 Wnt/β-连环蛋白通路的激活，从而抑制 EC 细胞的恶性表型和 EMT 过程。
