Department of Gastroenterology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, China.
Department of Hospital Infection Management, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Sep 6;51(9):900-907. doi: 10.1093/abbs/gmz077.
Currently, exosomes rich in RNAs and proteins are regarded as vital mediators of intercellular communication. Here, we aimed to explore the effects of exosomal miR-1290 in gastric cancer (GC) and understand its mechanism of action on GC progression. We first isolated exosomes from serum samples of GC patients and healthy people and characterized them by transmission electron microscopy. Then, we examined the expression level of miR-1290 contained in the exosomes by quantitative reverse-transcription polymerase chain reaction and found that exosomal miR-1290 was overexpressed in GC patients and cell lines. Promotion of proliferation, migration, and invasiveness of GC cells was noted after they were incubated with the isolated miR-1290-rich exosomes compared with incubation with a negative control. Furthermore, we predicted that naked cuticle homolog 1 (NKD1) mRNA is a direct target of miR-1290 and confirmed their interaction by a dual luciferase reporter assay. NKD1 overexpression attenuated the stimulatory effects of miR-1290 on GC cells. Collectively, our results suggest that exosomal miR-1290 enhances GC cell proliferation and invasion by targeting NKD1 mRNA and downregulating NKD1 expression. A better understanding of this process may facilitate the development of novel therapeutic agents for GC.
目前,富含 RNA 和蛋白质的外泌体被认为是细胞间通讯的重要介质。在这里,我们旨在探讨外泌体 miR-1290 在胃癌(GC)中的作用,并了解其对 GC 进展的作用机制。我们首先从 GC 患者和健康人血清样本中分离出外泌体,并通过透射电子显微镜对其进行了表征。然后,我们通过定量逆转录聚合酶链反应检测了外泌体中 miR-1290 的表达水平,发现 GC 患者和细胞系中外泌体 miR-1290 表达上调。与孵育阴性对照相比,孵育分离的富含 miR-1290 的外泌体后,GC 细胞的增殖、迁移和侵袭能力增强。此外,我们预测无角质蛋白同源物 1(NKD1)mRNA 是 miR-1290 的直接靶标,并通过双荧光素酶报告基因检测证实了它们的相互作用。NKD1 过表达可减弱 miR-1290 对 GC 细胞的刺激作用。综上所述,我们的研究结果表明,外泌体 miR-1290 通过靶向 NKD1 mRNA 并下调 NKD1 表达,增强 GC 细胞的增殖和侵袭能力。更好地了解这一过程可能有助于开发针对 GC 的新型治疗药物。