Zhang Shan, Yin Wan-Ling, Zhang Xin, Zhang Xiao-Yu
Department of Geriatrics, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China.
Department of Integrated Medicine (Houhu), The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
Mol Med Rep. 2017 Sep;16(3):3664-3672. doi: 10.3892/mmr.2017.6979. Epub 2017 Jul 14.
Gastric cancer is the fourth most common and the second leading cause of cancer mortality worldwide. The dysregulation of microRNAs has been demonstrated to be significant in gastric cancer carcinogenesis and progression due to changes in expression of their target genes. In the current study, microRNA‑455 (miR‑455) was identified to be significantly downregulated in gastric cancer tissue samples and cell lines. A low expression level of miR‑455 was correlated with the clinical stage, lymph node metastasis and tumor invasion in gastric cancer. Restoration of miR‑455 expression inhibited cell proliferation, migration and invasion of gastric cancer cells in vitro. Bioinformatic analysis and luciferase reporter assay revealed that miR‑455 directly targeted the 3'‑untranslated region of insulin‑like growth factor 1 receptor (IGF‑1R). In addition, the IGF‑1R mRNA expression level was increased in gastric cancer tissue samples and was inversely correlated with miR‑455 expression levels. Restoration of miR‑455 downregulated IGF‑1R mRNA and protein expression levels in gastric cancer cells. Furthermore, silencing of IGF‑1R significantly inhibited gastric cancer cell proliferation, migration and invasion, which was similar to the functions induced by miR‑455 overexpression. Thus, these results indicate that miR‑455 is involved in gastric cancer progression by directly targeting IGF‑1R and may serve as a novel therapeutic target for the treatment of gastric cancer.
胃癌是全球第四大常见癌症，也是癌症死亡的第二大主要原因。由于其靶基因表达的变化，微小RNA的失调已被证明在胃癌的发生和发展中具有重要意义。在本研究中，微小RNA-455（miR-455）被鉴定为在胃癌组织样本和细胞系中显著下调。miR-455的低表达水平与胃癌的临床分期、淋巴结转移和肿瘤侵袭相关。miR-455表达的恢复在体外抑制了胃癌细胞的增殖、迁移和侵袭。生物信息学分析和荧光素酶报告基因检测显示，miR-455直接靶向胰岛素样生长因子1受体（IGF-1R）的3'非翻译区。此外，IGF-1R mRNA表达水平在胃癌组织样本中升高，且与miR-455表达水平呈负相关。miR-455的恢复下调了胃癌细胞中IGF-1R mRNA和蛋白表达水平。此外，IGF-1R的沉默显著抑制了胃癌细胞的增殖、迁移和侵袭，这与miR-455过表达诱导的功能相似。因此，这些结果表明，miR-455通过直接靶向IGF-1R参与胃癌进展，并可能作为治疗胃癌的新治疗靶点。
