miR-107 通过下调 FAT4 来激活 PI3K-AKT 信号通路，从而调节胃癌细胞的生长和转移。

miR-107 regulates growth and metastasis of gastric cancer cells via activation of the PI3K-AKT signaling pathway by down-regulating FAT4.

机构信息

Department of Gastroenterology, Henan Provincial People's Hospital (Zhengzhou University People's Hospital, Fuwai Central China Cardiovascular Hospital), Zhengzhou, Henan Province, China.

Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China.

出版信息

Cancer Med. 2019 Sep;8(11):5264-5273. doi: 10.1002/cam4.2396. Epub 2019 Jul 12.

PURPOSE

To investigate the effect of miR-107 on the growth and metastasis of gastric cancer (GC) and elucidate the probable mechanisms.

METHODS

The expression of miR-107 and FAT4 in GC tissues and cells were detected using qRT-PCR. Bioinformatics and dual luciferase reporter gene assays were used to analyze the relationship between miR-107 and FAT4. miR-NC, miR-107 inhibitor, pcDNA3.1-FAT4 and siRNA-FAT4 were transfected into AGS and MKN-45 GC cell lines, respectively. The proliferation and migration abilities of GC cells after transfection were evaluated using the MTT assay, scratch test and transwell assay. The expression of epithelial-mesenchymal transition (EMT) markers: E-cadherin, N-cadherin, vimentin and related proteins of the PI3K/AKT signaling pathway were determined using western blot. The xenograft tumors of nude mice were observed to assess the tumorigenicity of GC cells in vivo.

RESULTS

MiR-107 was up-regulated, while FAT4 was down-regulated in GC tissues and cells (P < 0.05); FAT4 was targeted and negatively regulated by miR-107. Down-regulating miR-107 or up-regulating FAT4 inhibited the GC cells proliferation, migration, invasion and tumorigenicity, and could also reduce the expression of N-cadherin, vimentin, p-PI3K and p-Akt expression and up-regulate E-cadherin.

CONCLUSIONS

miR-107 promotes growth and metastasis in GC via activation of PI3K-AKT signaling by targeting FAT4, which may be a target for GC treatment.

目的

研究 miR-107 对胃癌（GC）生长和转移的影响，并阐明可能的机制。

方法

采用 qRT-PCR 检测 GC 组织和细胞中 miR-107 和 FAT4 的表达。利用生物信息学和双荧光素酶报告基因实验分析 miR-107 和 FAT4 之间的关系。分别将 miR-NC、miR-107 抑制剂、pcDNA3.1-FAT4 和 siRNA-FAT4 转染到 AGS 和 MKN-45 GC 细胞系中。采用 MTT 检测、划痕实验和 Transwell 检测转染后 GC 细胞的增殖和迁移能力。采用 Western blot 检测上皮间质转化（EMT）标志物：E-钙黏蛋白、N-钙黏蛋白、波形蛋白和 PI3K/AKT 信号通路相关蛋白的表达。观察裸鼠异种移植瘤，评估 GC 细胞体内致瘤性。