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MicroRNA-345 通过靶向 FOXQ1 抑制胃癌的转移和上皮-间充质转化。

MicroRNA-345 inhibits metastasis and epithelial-mesenchymal transition of gastric cancer by targeting FOXQ1.

机构信息

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.

出版信息

Oncol Rep. 2017 Nov;38(5):2752-2760. doi: 10.3892/or.2017.6001. Epub 2017 Sep 26.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d38/5780028/e78d416d5ac7/OR-38-05-2752-g00.jpg

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