General Surgery, Wuxi No. 4 People's Hospital, Affiliated Hospital of Jiangnan University, Wuxi, China.
Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):8861-8869. doi: 10.26355/eurrev_201910_19281.
Gastric cancer is the second highest mortality tumor and the fourth most common cancer worldwide that has high aggressiveness. MicroRNA-181d (miR-181d) has been established to be a tumor suppressor, by suppressing cell proliferation, cell cycle, and promoting apoptosis in several cancers. The purpose of this study is to explore the great roles of miR-181d in gastric cancer.
The Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were applied to calculate the mRNA and protein levels of miR-181d and genes. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays were utilized to measure the proliferative and invasive abilities. The Kaplan-Meier method was conducted to calculate the overall survival of gastric cancer patients.
MiR-181d was detected to be downregulated in gastric cancer tissues and cell lines compared to the peritumoral normal tissues and normal cell line. Downregulation of miR-181d predicted poor prognosis of gastric cancer patients. Cylindromatosis gene (CYLD) was overexpressed in gastric cancer tissues, which was confirmed to be a target gene of miR-181d in gastric cancer cell line HGC-27. Moreover, miR-181d inhibited the proliferation through CYLD/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway and inhibited the invasion-mediated epithelial-mesenchymal transition (EMT) in HGC-27 cells. In addition, overexpression of miR-181d suppressed tumor growth and xenograft tumorigenesis of HGC-27 cells in vivo.
MiR-181d functioned as a tumor suppressor by inhibiting the proliferation via PI3K/AKT pathway in vitro and in vivo and inhibiting invasion-mediated epithelial-mesenchymal transition (EMT) by targeting CYLD in gastric cancer. The newly identified miR-181d/CYLD axis provides novel insight into the pathogenesis of gastric cancer.
胃癌是全球死亡率第二高的肿瘤，也是第四常见的癌症，其侵袭性很强。MicroRNA-181d（miR-181d）已被证实是一种肿瘤抑制因子，可通过抑制细胞增殖、细胞周期并促进几种癌症的细胞凋亡。本研究旨在探讨 miR-181d 在胃癌中的重要作用。
应用实时定量聚合酶链反应（RT-qPCR）和 Western blot 检测 miR-181d 和基因的 mRNA 和蛋白水平。MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）和 Transwell 实验用于检测增殖和侵袭能力。Kaplan-Meier 法计算胃癌患者的总生存率。
与癌旁正常组织和正常细胞系相比，miR-181d 在胃癌组织和细胞系中表达下调。miR-181d 下调预示着胃癌患者预后不良。在胃癌组织中，Cylindromatosis 基因（CYLD）过表达，在胃癌细胞系 HGC-27 中被证实是 miR-181d 的靶基因。此外，miR-181d 通过 CYLD/磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）通路抑制增殖，并抑制 HGC-27 细胞中侵袭介导的上皮-间充质转化（EMT）。此外，miR-181d 的过表达抑制了体内 HGC-27 细胞的肿瘤生长和异种移植肿瘤生成。
miR-181d 通过在体外和体内抑制 PI3K/AKT 通路抑制增殖，并通过靶向 CYLD 抑制侵袭介导的上皮-间充质转化（EMT），发挥肿瘤抑制因子的作用。新鉴定的 miR-181d/CYLD 轴为胃癌的发病机制提供了新的见解。
