Department of medical Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, China.
Department of medical Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, China.
Biomed Pharmacother. 2018 Jan;97:473-480. doi: 10.1016/j.biopha.2017.10.069. Epub 2017 Nov 6.
The reliable truth that exceptional miRNAs contribute to gastric cancer (GC) development and progression had been testified by researchers. However, the roles of various miRNAs in GC remain to be determined. In present research, we firmly believed that the expression of miR-599 in GC cell lines and tissues was declined. Clinical analysis disclosed that poor prognostic features, which incorporated lymph node metastasis and advanced TNM stage, could be expressively influenced by down-regulation of miR-599. For 5-year predicted-survival of GC patients, miR-599 was also confirmed to be a specialty prognostic marker. Notably, overmuch expression of miR-599 restricted cell migration, invasion and EMT progress, while down-regulated miR-599 reversed the effect in vitro and in vivo. Through directly binding to the 3'-UTR, miR-599 could possess EIF5A2 efficiently. In clinical samples of GC, miR-599 was inversely correlated with EIF5A2, which was upregulated in GC. The influence of miR-599 on migration, invasion and EMT progress could be partially discarded through alternation of EIF5A2 expression. Conclusively, our results manifested that miR-599 possessed the function of tumor suppressor gene in regulating EMT and metastasizing GC via targeting EIF5A2. Therefore, miR-599 has the capacity to become a therapeutic target and prognostic marker for GC.
研究人员已经证实，特殊的 miRNA 有助于胃癌（GC）的发展和进展是可靠的事实。然而，各种 miRNA 在 GC 中的作用仍有待确定。在目前的研究中，我们坚信 miR-599 在 GC 细胞系和组织中的表达下降。临床分析表明，miR-599 的下调显著影响了不良的预后特征，包括淋巴结转移和晚期 TNM 分期。对于 GC 患者的 5 年预测生存率，miR-599 也被证实是一种特殊的预后标志物。值得注意的是，miR-599 的过表达限制了细胞迁移、侵袭和 EMT 进展，而下调 miR-599 在体外和体内逆转了这种作用。通过直接结合 3'-UTR，miR-599 可以有效地结合 EIF5A2。在 GC 的临床样本中，miR-599 与 EIF5A2 呈负相关，EIF5A2 在 GC 中上调。通过改变 EIF5A2 的表达，可以部分消除 miR-599 对迁移、侵袭和 EMT 进展的影响。总之，我们的结果表明，miR-599 通过靶向 EIF5A2 ，在调节 EMT 和转移性 GC 中具有肿瘤抑制基因的功能。因此，miR-599 有潜力成为 GC 的治疗靶点和预后标志物。
