POU2F1 抑制 miR-29b1/a 簇介导的 PIK3R1 和 PIK3R3 表达抑制,从而调节胃癌细胞的侵袭和迁移。
POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration.
发表日期:2024 Aug 26
作者:
Yizhi Xiao, Ping Yang, Wushuang Xiao, Zhen Yu, Jiaying Li, Xiaofeng Li, Jianjiao Lin, Jieming Zhang, Miaomiao Pei, Linjie Hong, Juanying Yang, Zhizhao Lin, Ping Jiang, Li Xiang, Guoxin Li, Xinbo Ai, Weiyu Dai, Weimei Tang, Jide Wang
来源:
CHINESE MEDICAL JOURNAL
摘要:
转录因子 POU2F1 调节肿瘤中 microRNA 的表达水平。然而,胃癌(GC)中POU2F1调节的miR-29b1/a簇仍然未知。使用逆转录聚合酶链反应(PCR)、蛋白质印迹、免疫组织化学和RNA原位杂交评估GC细胞中的基因表达。进行免疫共沉淀以评估蛋白质相互作用。进行Transwell迁移和侵袭实验来研究GC细胞的生物学行为。在 GC 细胞中进行了 3'-UTR 研究的 MiR-29b1/a 簇启动子分析和荧光素酶活性测定。在裸鼠中评估体内肿瘤转移。POU2F1 在 GC 细胞系中过表达并与 miR-29b1/a 簇启动子结合。在 GC 组织中,POU2F1 上调,而成熟 miR-29b-3p 和 miR-29a-3p 下调。 POU2F1 通过抑制体外和体内 miR-29b-3p 或 miR-29a-3p 表达来促进 GC 转移。此外,PIK3R1和/或PIK3R3是miR-29b-3p和/或miR-29a-3p的直接靶标,并且PIK3R1或PIK3R3的异位表达逆转成熟miR-29b-3p和/或miR-29a的抑制作用-3p对GC细胞转移和侵袭的影响。此外,PIK3R1 与 PIK3R3 的相互作用促进迁移和侵袭,miR-29b-3p、miR-29a-3p、PIK3R1 和 PIK3R3 通过磷脂酰肌醇 3-激酶/蛋白激酶 B/雷帕霉素的哺乳动物靶标调节迁移和侵袭。 GC 细胞中的 PI3K/Akt/mTOR) 通路。此外,GC组织样本中POU2F1、PIK3R1和PIK3R3的表达水平与miR-29b-3p和miR-29a-3p的表达水平呈负相关。 POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1信号轴调节肿瘤进展,可能是 GC 的一个有前途的治疗靶点。版权所有 © 2024 中华医学会,由 Wolters Kluwer, Inc. 根据 CC-BY-NC-ND 许可制作。
The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown.Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice.POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo. Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p, and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p, miR-29a-3p, PIK3R1, and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1, PIK3R1, and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples.The POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.