炭疽毒素受体2表达受miR-145-5p调控在胰腺癌的作用机制研究

Mechanism of anthrax toxin receptor 2 expression regulated by miR-145-5p in pancreatic cancer

摘要:

目的 探讨炭疽毒素受体2（anthrax toxin receptor 2，ANTXR2）在胰腺癌组织和细胞中的表达、临床意义和细胞功能，验证miR-145-5p在胰腺癌细胞中调控ANTXR2的作用机制。方法 分析GEO和TCGA数据库中胰腺癌的转录数据和临床数据。通过CCK-8实验、流式细胞术、划痕实验和Transwell实验进行细胞功能验证。采用miRNA靶点预测数据库反向预测可能通过ceRNA机制抑制ANTXR2表达的miRNA，并使用双荧光素酶报告实验进行验证。结果 ANTXR2在胰腺癌组织和细胞中的表达均上调（均P<0.05），ANTXR2上调预示着原发肿瘤等级（P<0.05）、肿瘤细胞分化等级（P<0.05）和总体生存期（P<0.05，HR=1.72）均较差。ANTXR2可以促进胰腺癌细胞增殖、迁移和侵袭（均P<0.05）。ANTXR2是miR-145-5p下游的靶标（P<0.01），miR-145-5p可以通过抑制ANTXR2的表达抑制胰腺癌细胞增殖、迁移和侵袭。结论 ANTXR2在胰腺癌组织和细胞中过表达，促进胰腺癌细胞增殖、迁移和侵袭，且与患者预后有关。miR-145-5p通过调控ANTXR2的表达抑制其促癌作用。

Abstract:

Objective To investigate the expression，clinical significance and cellular functions of anthrax toxin receptor 2（ANTXR2）in pancreatic cancer tissues and cells and to validate the mechanism of miR-145-5p in regulating ANTXR2 in pancreatic cancer cells.Methods Analysis of transcriptional and clinical data from the GEO and TCGA databases for pancreatic cancer was made. Cellular function was validated by CCK-8 assay，flow cytometry，wound healing experiment and Transwell assay. The miRNA target prediction database was used to reversely predict miRNAs that might inhibit ANTXR2 expression through the ceRNA mechanism，and it was validated using dual luciferase reporter assays.Results ANTXR2 expression was upregulated in both pancreatic cancer tissues and cells（all P<0.05），and ANTXR2 upregulation predicted poorer primary tumor grade（P<0.05），tumor cell differentiation grade（P<0.05） and overall survival（P<0.05，HR=1.72）. ANTXR2 inhibited the cell proliferation，migration and invasion（all P<0.05）. ANTXR2 was a target of miR-145-5p（P<0.01），and miR-145-5p could inhibit the proliferation，migration and invasion of pancreatic cancer cells by suppressing the expression of ANTXR2.Conclusion ANTXR2 is overexpressed in pancreatic cancer tissues and cells，can promote proliferation，migration and invasion of pancreatic cancer cells and is associated with patient prognosis. miR-145-5p can inhibit the pro-cancerous effects of ANTXR2 by regulating its expression.