Department of Medical Imaging, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China.
Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):8833-8840. doi: 10.26355/eurrev_201910_19278.
DJ-1 is a negative regulator of PTEN and plays a role in tumorigenesis. Abnormal miR-203 expression is associated with pancreatic cancer. Bioinformatics analysis showed a targeted relationship between miR-203 and DJ-1 3'-UTR. This study investigated whether miR-203 regulates DJ-1 expression and its role in pancreatic cancer cell proliferation, apoptosis, and cisplatin (DDP) resistance.
The Dual-Luciferase reporter gene assay validated the targeted regulation between miR-203 and DJ-1. The DDP-resistant cell line SW1990/DDP was established and divided into miR-NC group and miR-203 mimic group followed by analysis of the expression of DJ-1, PTEN and p-AKT, cell apoptosis, and proliferation.
There was a targeted relationship between miR-203 and DJ-1 mRNA. The expression of miR-203 in SW1990/DDP cells was significantly lower than that in SW1990 cells, while the expression of DJ-1 mRNA and protein was significantly higher than that in SW1990 cells. Compared with miR-NC group, the expression of DJ-1 and p-AKT protein in SW1990/DDP cells was significantly decreased in miR-203 mimic transfection group, while the expression of PTEN was significantly increased with increased cell apoptosis and decreased cell proliferation, as well as reduced DDP resistance.
The decreased expression of miR-203 and the increased expression of DJ-1 is associated with drug resistance in pancreatic cancer cells. Elevated miR-203 can inhibit the expression of DJ-1, affect the activity of PTEN-PI3K/AKT pathway, inhibit the proliferation of pancreatic cancer cells, induce cell apoptosis, and reduce DDP resistance of pancreatic cancer cells.
DJ-1 是 PTEN 的负调控因子,在肿瘤发生中起作用。异常的 miR-203 表达与胰腺癌有关。生物信息学分析显示 miR-203 与 DJ-1 3'-UTR 之间存在靶向关系。本研究探讨了 miR-203 是否调节 DJ-1 表达及其在胰腺癌细胞增殖、凋亡和顺铂(DDP)耐药中的作用。
双荧光素酶报告基因检测验证了 miR-203 与 DJ-1 之间的靶向调控关系。建立 DDP 耐药细胞系 SW1990/DDP,并分为 miR-NC 组和 miR-203 模拟物组,然后分析 DJ-1、PTEN 和 p-AKT 的表达、细胞凋亡和增殖。
miR-203 与 DJ-1 mRNA 之间存在靶向关系。SW1990/DDP 细胞中 miR-203 的表达明显低于 SW1990 细胞,而 DJ-1 mRNA 和蛋白的表达明显高于 SW1990 细胞。与 miR-NC 组相比,miR-203 模拟转染组 SW1990/DDP 细胞中 DJ-1 和 p-AKT 蛋白的表达明显降低,而 PTEN 的表达明显增加,细胞凋亡增加,细胞增殖减少,DDP 耐药性降低。
miR-203 表达降低和 DJ-1 表达增加与胰腺癌细胞耐药有关。上调 miR-203 可抑制 DJ-1 的表达,影响 PTEN-PI3K/AKT 通路的活性,抑制胰腺癌细胞增殖,诱导细胞凋亡,降低胰腺癌细胞对 DDP 的耐药性。