长链非编码 RNA MIAT 通过调控 miR-141/DDX5 通路促进胃癌生长和转移。
Long non-coding RNA MIAT promotes gastric cancer growth and metastasis through regulation of miR-141/DDX5 pathway.
机构信息
Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China.
Department of Reproductive Medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China.
出版信息
J Exp Clin Cancer Res. 2018 Mar 14;37(1):58. doi: 10.1186/s13046-018-0725-3.
BACKGROUND
The objective of this study was to investigate the role and mechanism of long non-coding RNA MIAT in gastric cancer (GC).
METHODS
Real-time PCR was used to determine MIAT level in 120 GC tissues, and in two gastric cancer cell lines. The clinicopathological characteristics of MIAT in GC patients were analyzed. Small interfering RNA specific for MIAT (si-MIAT) and lentivector for si-MIAT was performed to down-regulate MIAT expression in GC cells and in animal tumor model, respectively. The interaction of MIAT and miR-141 was measured by RNA pull-down assay and RNA immunoprecipitation. The biological function of si-MIAT on GC cell growth and metastasis were explored through flow cytometry assay, invasion and migration assay in vitro.
RESULTS
MIAT was highly expressed in GC tissues and cell lines and correlated with differentiation degree, TNM stage, distant metastasis, and lymph node metastasis. MIAT knockdown inhibited GC growth and metastasis both in vitro and in vivo. Furthermore, MIAT acted as miR-141 sponge and regulated its target gene DDX5 expression. In BGC-823 and MGC-803 cells with si-MIAT, DDX5 overexpression resulted in an increase of cell proliferation, migration and invasion.
CONCLUSIONS
Our data indicated that MIAT played an oncogenic role in GC growth and metastasis, and could serve as a novel molecular target for treating GC.
背景
本研究旨在探讨长链非编码 RNA MIAT 在胃癌（GC）中的作用和机制。
方法
采用实时 PCR 检测 120 例 GC 组织和两种胃癌细胞系中的 MIAT 水平。分析 MIAT 在 GC 患者中的临床病理特征。采用特异性靶向 MIAT 的小干扰 RNA（si-MIAT）和慢病毒载体下调 GC 细胞和动物肿瘤模型中的 MIAT 表达。通过 RNA 下拉实验和 RNA 免疫沉淀实验测定 MIAT 和 miR-141 的相互作用。通过流式细胞术、体外侵袭和迁移实验探讨 si-MIAT 对 GC 细胞生长和转移的生物学功能。
结果
MIAT 在 GC 组织和细胞系中高表达，与分化程度、TNM 分期、远处转移和淋巴结转移相关。MIAT 敲低抑制 GC 的体外和体内生长和转移。此外，MIAT 作为 miR-141 的海绵体调节其靶基因 DDX5 的表达。在 BGC-823 和 MGC-803 细胞中，si-MIAT 转染后过表达 DDX5 可促进细胞增殖、迁移和侵袭。
结论
我们的数据表明，MIAT 在 GC 的生长和转移中发挥致癌作用，可作为治疗 GC 的新分子靶点。
Zotero 插件