Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China.
Int J Oncol. 2019 Mar;54(3):845-858. doi: 10.3892/ijo.2019.4680. Epub 2019 Jan 8.
Gastric cancer (GC) is one of the most common and fatal types of cancers worldwide and the specific mechanism has not been completely elucidated. microRNA (miR)‑3664‑5P has rarely been studied and the aim of the present study was to assess an association between miR‑3664‑5P and GC. Differences in miR‑3664‑5P expression in 100 GC (0.1846±0.08276) and paired normal tissues (0.4382±0.1595) were detected using reverse transcription‑quantitative polymerase chain reaction assays (P<0.001). 5‑Ethynyl‑2‑deoxyuridine, Cell Counting Kit‑8, transwell and flow cytometry assays were performed in vitro and the results were further verified using a mouse xenotransplantation and a lung metastasis model in vivo. miR‑3664‑5P was significantly downregulated in GC tissues when compared with normal tissues and positively associated with the prognosis of patients with GC (P<0.001). Overexpression of miR‑3664‑5P suppressed and miR‑3664‑5P knockdown promoted the proliferation and metastasis of GC cells in vitro and in vivo. Following the application of bioinformatic algorithms and luciferase reporter assays, metadherin (MTDH) was confirmed as the target gene of miR‑3664‑5P. miR‑3664‑5P reduced MTDH expression and downregulated the nuclear factor (NF)‑κB signaling pathway. Rescue experiments demonstrated that suppression of MTDH restored the effect of miR‑3664‑5P inhibitors on GC cell lines. The results suggested that miR‑3664‑5P suppressed the proliferation and metastasis of GC cells by attenuating the NF‑κB signaling pathway via MTDH targeting. Consequently, miR‑3664‑5P may have potential to be an independent prognostic factor and biomarker in GC.
胃癌(GC)是全球最常见和致命的癌症类型之一,但其具体机制尚未完全阐明。microRNA(miR)-3664-5P 的研究甚少,本研究旨在评估 miR-3664-5P 与 GC 之间的关联。采用逆转录-定量聚合酶链反应检测 100 例 GC(0.1846±0.08276)和配对正常组织(0.4382±0.1595)中 miR-3664-5P 的表达差异(P<0.001)。体外进行 5-乙炔基-2-脱氧尿苷、细胞计数试剂盒-8、Transwell 和流式细胞术检测,进一步通过体内小鼠异种移植和肺转移模型验证。GC 组织中 miR-3664-5P 的表达明显低于正常组织,且与 GC 患者的预后呈正相关(P<0.001)。miR-3664-5P 过表达抑制、miR-3664-5P 敲低促进 GC 细胞的增殖和转移。应用生物信息学算法和荧光素酶报告基因检测后,确定了 MTDH 为 miR-3664-5P 的靶基因。miR-3664-5P 降低 MTDH 表达并下调核因子(NF)-κB 信号通路。挽救实验表明,抑制 MTDH 恢复了 miR-3664-5P 抑制剂对 GC 细胞系的作用。结果表明,miR-3664-5P 通过靶向 MTDH 减弱 NF-κB 信号通路抑制 GC 细胞的增殖和转移。因此,miR-3664-5P 可能成为 GC 的独立预后因子和生物标志物。