Department of Enterochirurgia, Huaian First People's Hospital, Huaian, Jiangsu 223300, P.R. China.
Department of Gastroenterological Surgery, Huaian First People's Hospital, Huaian, Jiangsu 223300, P.R. China.
Oncol Rep. 2017 Nov;38(5):2752-2760. doi: 10.3892/or.2017.6001. Epub 2017 Sep 26.
MicroRNAs (miRNAs) are a group of critical players in gastric cancer (GC). Among numerous cancer-related miRNAs, the expression level and functional role of miR-345 in GC has not been investigated. This study showed that miR-345 expression was decreased in GC. Decreased expression level of miR-345 was associated with occurrence of lymph metastasis and advanced TNM stage of GC patients. Patients with low expression level of miR-345 had reduced overall survival (OS) and disease-free survival (DFS). In vitro experiments showed that miR-345 could inhibit the migration and invasion of GC cells. In vivo experiments showed that miR-345 knockdown could promote lung metastasis of GC cells in nude mice. miR-345 was found to prevent the metastasis by inhibiting epithelial-mesenchymal transition (EMT) of GC cells. Furthermore, FOXQ1 was confirmed to be the downstream target of miR-345 in GC cells. Forced expression of FOXQ1 could reverse the inhibitory effects of miR-345 on GC metastasis, while knockdown of FOXQ1 prevented the promoting effects of miR-345 knockdown on GC metastasis. In summary, this study demonstrates miR-345 is a promising biomarker and therapeutic target in GC.
微小 RNA(miRNAs)是胃癌(GC)中一类重要的调控因子。在众多与癌症相关的 miRNAs 中,miR-345 在 GC 中的表达水平和功能作用尚未被研究。本研究表明 miR-345 在 GC 中表达下调。miR-345 表达下调与 GC 患者发生淋巴转移和较晚的 TNM 分期有关。miR-345 低表达的患者总生存期(OS)和无病生存期(DFS)缩短。体外实验表明 miR-345 可抑制 GC 细胞的迁移和侵袭。体内实验表明 miR-345 敲低可促进裸鼠 GC 细胞的肺转移。研究发现 miR-345 通过抑制 GC 细胞上皮-间质转化(EMT)来预防转移。此外,在 GC 细胞中证实 FOXQ1 是 miR-345 的下游靶基因。过表达 FOXQ1 可逆转 miR-345 对 GC 转移的抑制作用,而敲低 FOXQ1 则可阻止 miR-345 敲低对 GC 转移的促进作用。总之,本研究表明 miR-345 是 GC 中有前途的生物标志物和治疗靶标。