Department of Gastrointestinal Surgery, Jining No. 1 People's Hospital, Jining, China.
Neoplasma. 2018 Sep 19;65(5):769-778. doi: 10.4149/neo_2018_171204N794. Epub 2018 Jun 17.
Gastric cancer is the main leading cause of cancer-related death worldwide. The aberrant expression of paternally expressed gene 10 (PEG10) is involved in development of a range of cancers. However, the potential biological function and the underling mechanism of PEG10 in human gastric carcinoma are still unknown. Knocking down LncRNA PEG10 might represent a promising therapeutic strategy for the treatment of gastric cancer. The expression of PEG10, miR-3200, and AEG1 in human gastric carcinoma NCI-N87 cells were altered by cell transfection assay. Cell viability, migration, invasion, and apoptosis were determined by trypan blue exclusion, Transwell assay, and flow cytometric analysis, respectively. RNA and protein expression level of gene was analyzed by real-time PCR and Western blot. Luciferase reporter assay was conducted to determine the target gene of miR-3200. JNK and Wnt signal pathway protein expressions were tested by Western blot. The up-regulation of PEG10 was found in clinical samples. PEG10 knockdown effectively inhibited gastric carcinoma cell viability, migration, and invasion, but promoted cell apoptosis. This tumor-suppressing effect of PEG10 knockdown might be realized by up-regulating miR-3200 in vitro and in vivo. AEG1 was a direct target gene of miR-3200. Moreover, miR-3200 might suppress NCI-N87 cells by negative regulating AEG1. Up-regulating miR-3200 effectively blocked JNK and Wnt pathways likely via down-regulating AEG1. PEG10 knockdown played a carcinostatic role via up-regulating miR-3200 and further regulating AEG1 in gastric carcinoma cells, during which process, JNK pathway and Wnt pathway were blocked.
胃癌是全球癌症相关死亡的主要原因。父系表达基因 10（PEG10）的异常表达与多种癌症的发生有关。然而，PEG10 在人胃癌中的潜在生物学功能和作用机制尚不清楚。敲低 LncRNA PEG10 可能代表治疗胃癌的一种有前途的治疗策略。通过细胞转染实验改变人胃癌 NCI-N87 细胞中 PEG10、miR-3200 和 AEG1 的表达。通过台盼蓝排斥试验、Transwell 试验和流式细胞术分析分别测定细胞活力、迁移、侵袭和细胞凋亡。通过实时 PCR 和 Western blot 分析基因的 RNA 和蛋白表达水平。通过荧光素酶报告试验确定 miR-3200 的靶基因。通过 Western blot 检测 JNK 和 Wnt 信号通路蛋白的表达。在临床样本中发现 PEG10 上调。PEG10 敲低有效抑制胃癌细胞活力、迁移和侵袭，但促进细胞凋亡。PEG10 敲低的这种肿瘤抑制作用可能是通过体外和体内上调 miR-3200 实现的。AEG1 是 miR-3200 的直接靶基因。此外，miR-3200 可能通过负调控 AEG1 来抑制 NCI-N87 细胞。上调 miR-3200 可通过下调 AEG1 有效阻断 JNK 和 Wnt 途径。PEG10 敲低通过上调 miR-3200 并进一步调节胃癌细胞中的 AEG1 发挥抗癌作用，在此过程中阻断 JNK 途径和 Wnt 途径。
