Department of Hepato-Biliary-Pancreatic Surgery, Tenth Peoples' Hospital, School of Medicine, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
Cancer Cell Int. 2013 Jul 8;13(1):68. doi: 10.1186/1475-2867-13-68.
MicroRNAs are a class of small non-coding RNAs that play an important role in various human tumor initiation and progression by regulating gene expression negatively. The aim of this study was to investigate the effect of miR-214 on cell proliferation, migration and invasion, as well as the functional connection between miR-214 and PTEN in gastric cancer.
miR-214 and PTEN expression was determined in gastric cancer and matched normal tissues, and human gastric cancer cell lines by quantitative real-time PCR. The roles of miR-214 in cell proliferation, migration and invasion were analyzed with anti-miR-214 transfected cells. In addition, the regulation of PTEN by miR-214 was evaluated by Western blotting and luciferase reporter assays.
miR-214 was noted to be highly overexpressed in gastric cancer tissues and cell lines using qRT-PCR. The expression level of miR-214 is significantly associated with clinical progression and poor prognosis according to the analysis of the clinicopathologic data. We also found that the miR-214 levels are inversely correlated with PTEN in tumor tissues. And PTEN expression level is also associated with metastasis and invasion of gastric cancer. In addition, knockdown of miR-214 could significantly inhibit proliferation, migration and invasion of gastric cancer cells. Moreover, we demonstrate that PTEN is regulated negatively by miR-214 through a miR-214 binding site within the 3'-UTR of PTEN at the posttranscriptional level in gastric cancer cells.
These findings indicated that miR-214 regulated the proliferation, migration and invasion by targeting PTEN post-transcriptionally in gastric cancer. It may be a novel potential therapeutic agent for gastric cancer.
microRNAs 是一类小的非编码 RNA,通过负向调控基因表达,在各种人类肿瘤的起始和进展中发挥重要作用。本研究旨在探讨 miR-214 对胃癌细胞增殖、迁移和侵袭的影响,以及 miR-214 与 PTEN 之间的功能关系。
采用实时定量 PCR 检测胃癌及配对正常组织和人胃癌细胞系中 miR-214 和 PTEN 的表达。用抗 miR-214 转染细胞分析 miR-214 对细胞增殖、迁移和侵袭的作用。此外,通过 Western blot 和荧光素酶报告基因实验评估 miR-214 对 PTEN 的调控作用。
qRT-PCR 结果显示 miR-214 在胃癌组织和细胞系中高表达。根据临床病理数据分析,miR-214 的表达水平与临床进展和预后不良显著相关。我们还发现 miR-214 的水平与肿瘤组织中的 PTEN 呈负相关。PTEN 的表达水平也与胃癌的转移和侵袭有关。此外,下调 miR-214 可显著抑制胃癌细胞的增殖、迁移和侵袭。此外,我们证明 miR-214 通过靶向胃癌细胞中 PTEN 的 3'-UTR 上的 miR-214 结合位点在转录后水平负调控 PTEN。
这些发现表明 miR-214 通过靶向 PTEN 负调控胃癌中的增殖、迁移和侵袭。它可能是一种新的潜在的胃癌治疗靶点。