Department of Gastroenterology, Weifang People's Hospital, Weifang, China.
Outpatient Department, Liaocheng Chiping District People's Hospital, Liaocheng, China.
Kaohsiung J Med Sci. 2021 Jul;37(7):562-571. doi: 10.1002/kjm2.12383. Epub 2021 May 5.
S100 calcium binding protein P (S100P) and miR-495 are aberrantly expressed and exert essential roles in cancers. However, the mechanisms of miR-495-S100P in pancreatic cancer are yet to be illustrated. Thus, we explored the regulatory functions of miR-495-S100P axis in pancreatic adenocarcinoma cells growth and invasion. In this study, we identified that S100P was upregulated in pancreatic adenocarcinoma by bioinformatics analysis of the GEO (Gene Expression Omnibus database) microarray dataset (GSE16515). Western blotting and luciferase reporter gene analysis exhibited that miR-495 negatively determined the level of S100P via binging to its 3'-untranslated regions (3'-UTRs). A series of functional experiments indicated that upregulation of miR-495 or S100P knockdown suppressed pancreatic adenocarcinoma cells proliferation, invasion, and promoted apoptosis. Furthermore, the expression of S100P was negatively associated with the level of miR-495 in The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma case-cohort. Besides, reintroduction of S100P debilitated the anti-cancer action of miR-495 in pancreatic adenocarcinoma cells. Our data indicated that miR-495 performed suppressive roles in pancreatic adenocarcinoma through targeting S100P.
S100 钙结合蛋白 P（S100P）和 miR-495 表达异常，在癌症中发挥重要作用。然而，miR-495-S100P 在胰腺癌中的作用机制尚不清楚。因此，我们探讨了 miR-495-S100P 轴在胰腺腺癌细胞生长和侵袭中的调节功能。在这项研究中，我们通过对 GEO（基因表达综合数据库）微阵列数据集（GSE16515）的生物信息学分析，确定 S100P 在胰腺腺癌中上调。Western blot 和荧光素酶报告基因分析表明，miR-495 通过结合其 3'-非翻译区（3'-UTRs）负向调节 S100P 的水平。一系列功能实验表明，上调 miR-495 或 S100P 敲低抑制胰腺腺癌细胞增殖、侵袭，并促进细胞凋亡。此外，S100P 的表达与 TCGA 胰腺腺癌病例队列中 miR-495 的水平呈负相关。此外，S100P 的重新引入削弱了 miR-495 在胰腺腺癌细胞中的抗癌作用。我们的数据表明，miR-495 通过靶向 S100P 在胰腺腺癌中发挥抑制作用。
