Queen Mary Institute, Nanchang University, Nanchang, China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1513-1519. doi: 10.26355/eurrev_201902_17109.
To explore the influence of exosome-derived micro-ribonucleic acid (miR)-21 on chemotherapy resistance of esophageal cancer and its mechanism.
Human esophageal cancer TE-1 and Eca109/DDP cell lines and human normal esophageal Het-1A cells were cultured, and the exosomes were extracted from cells. After miR-21 was inhibited with an inhibitor and overexpressed with miRNA mimics combined with cisplatin, the cell viability was detected via cell counting kit-8 (CCK-8), the interaction between miR-21 and programmed cell death 4 (PDCD4) was detected via dual-luciferase reporter gene assay, and the changes in the protein level were detected via Western blotting.
The expression level of exosome-derived miR-21 in esophageal cancer cells was higher than that in normal esophageal cells, and it was the highest in cisplatin-resistant esophageal cancer cells. After treatment with cisplatin, miR-21 overexpression significantly reduced the invasion ability of esophageal cancer cells. After miR-21 overexpression, the sensitivity of esophageal cancer cells to cisplatin was lowered. MiR-21 interacted with the 3'-untranslated region (UTR) of PDCD4. Moreover, the miR-21 overexpression significantly down-regulated the mRNA and protein levels of PDCD4 in cells.
MiR-21 affects the sensitivity of esophageal cancer to cisplatin through targeting PDCD4.
探讨外泌体来源的 microRNA-21(miR-21)对食管癌化疗耐药的影响及其机制。
培养人食管癌细胞 TE-1 和 Eca109/DDP 及人正常食管 Het-1A 细胞,提取细胞外泌体。用抑制剂抑制 miR-21 并结合顺铂过表达 miR-21 模拟物后,通过细胞计数试剂盒-8(CCK-8)检测细胞活力,通过双荧光素酶报告基因检测 miR-21 与程序性细胞死亡蛋白 4(PDCD4)的相互作用,通过 Western blot 检测蛋白水平的变化。
食管癌细胞中外泌体衍生的 miR-21 表达水平高于正常食管细胞,在顺铂耐药的食管癌细胞中最高。用顺铂处理后,miR-21 过表达显著降低了食管癌细胞的侵袭能力。miR-21 过表达后,食管癌细胞对顺铂的敏感性降低。miR-21 与 PDCD4 的 3′非翻译区(UTR)相互作用。此外,miR-21 过表达显著下调了细胞中 PDCD4 的 mRNA 和蛋白水平。
miR-21 通过靶向 PDCD4 影响食管癌对顺铂的敏感性。