Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, PR China; College of Health Sciences, Jiangsu Normal University, Xuzhou 221116, PR China.
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, PR China.
Int J Biochem Cell Biol. 2018 Sep;102:59-70. doi: 10.1016/j.biocel.2018.06.007. Epub 2018 Jun 25.
MicroRNAs (miRNAs), a novel class of important gene-regulatory molecules, correlates with tumor growth, invasion, metastasis, and chemo resistance in gastric cancer (GC). Microarray analysis revealed that aberrant expressed microRNA-17 (miR-17) and DEDD were identified in GC. DEDD has been found to act as an endogenous suppressor of tumor growth and metastasis through epithelial-mesenchymal transition (EMT) process. However, the role of miRNA-17 (miR-17) has not been clearly evaluated in GC, thereby a series of in vitro experiments were performed in this study. The levels of miR-17 and DEDD in GC tissues from patients diagnosed with GC and in five GC cell lines (SGC-7901, MKN-45, HGC-27, BGC823, and AGS) were detected. It was found that miR-17 up-regulated and DEDD down-regulated in GC, and SGC-7901 and AGS cells were adopted for the in vitro cell experiments, in which the expression of miR-17 or DEDD was regulated by transfection. DEDD was validated to be a target gene of miR-17. Inhibition of miR-17 impaired EMT in GC cells. In addition, transwell assay and scratch test results revealed that inhibition of miR-17 hindered GC cell invasion and migration. Moreover, inhibition of miR-17 reduced resistance to cisplatin- or 5-Fu in GC cells and induced cisplatin- or 5-Fu-treated GC cell apoptosis, which evaluated by using CCK-8 and flow cytometry assays. From the short review above, the key findings emerge that inhibition of miR-17 may have tumor suppressive effects on GC and enhance its chemosensitivity by promoting DEDD, highlighting a novel target for GC therapy.
微小 RNA（miRNAs）是一类重要的基因调控分子，与胃癌（GC）的肿瘤生长、侵袭、转移和化疗耐药相关。微阵列分析显示，GC 中存在异常表达的 microRNA-17（miR-17）和 DEDD。已经发现 DEDD 通过上皮-间质转化（EMT）过程作为肿瘤生长和转移的内源性抑制物发挥作用。然而，miR-17 在 GC 中的作用尚未得到明确评估，因此本研究进行了一系列体外实验。检测了诊断为 GC 的患者的 GC 组织和 5 种 GC 细胞系（SGC-7901、MKN-45、HGC-27、BGC823 和 AGS）中 miR-17 和 DEDD 的水平。结果发现，GC 中 miR-17 上调，DEDD 下调，选择 SGC-7901 和 AGS 细胞进行体外细胞实验，通过转染调节 miR-17 或 DEDD 的表达。验证 DEDD 是 miR-17 的靶基因。抑制 miR-17 可破坏 GC 细胞中的 EMT。此外，Transwell assay 和划痕试验结果表明，抑制 miR-17 可抑制 GC 细胞侵袭和迁移。此外，抑制 miR-17 降低了 GC 细胞对顺铂或 5-Fu 的耐药性，并通过 CCK-8 和流式细胞术检测诱导顺铂或 5-Fu 处理的 GC 细胞凋亡。综上所述，抑制 miR-17 可能对 GC 具有肿瘤抑制作用，并通过促进 DEDD 提高其化疗敏感性，为 GC 治疗提供了一个新的靶点。
