miR-106b通过在体外和体内靶向ALEX1促进早期胃癌转移。

miR-106b Promotes Metastasis of Early Gastric Cancer by Targeting ALEX1 in Vitro and in Vivo.

作者信息

Zhu Zhenglun, Yang Qiumeng, Zhang Benyan, Wu Wei, Yuan Fei, Zhu Zhenggang

机构信息

Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Cell Physiol Biochem. 2019;52(3):606-616. doi: 10.33594/000000043.

DOI:10.33594/000000043

PMID:30907988

Abstract

BACKGROUND/AIMS: Aberrant expression of miR-106b is a specific symptom of many solid carcinomas. Overexpression of miR-106b has been observed in gastric cancer. The effect of miR-106b on gastric cancer has been investigated in different cell culture models. However, the effect of miR-106b on metastasis of early gastric cancer (EGC) remains unknown.

METHODS

In the study, qRT-PCR, FISH, western blot, luciferase reporter assay, migration and invasion assays, flow cytometry and TUNEL staining were used to investigate the effect of miR-106b on metastasis of EGC.

RESULTS

To explore the function of miR-106b in EGC, we investigated the downstream signaling of miR-106b and found that ALEX1 was a direct target of miR-106 in gastric cancer cells. Up-regulation of ALEX1 effectively rescued the cell apoptosis induced by miR-106b inhibitor and promoted the expression levels of phosphorylation of JAK1 and STAT3. Moreover, overexpression of JAK1 reduced the cell apoptosis induced by miR-106b inhibitor and decreased the expression levels of the apoptotic proteins in gastric cancer cells. Furthermore, down-regulation of miR-106b promoted apoptosis of gastric cancer cells via inhibiting JAK1/STAT3 signaling pathway in vitro and in vivo. In addition, GLPG0643, a JAK1 inhibitor, enhanced the inhibitory effect of miR-106b inhibitor on gastric cancer growth in vivo.

CONCLUSION

These findings provided a potential therapeutic manner for the treatment of metastasis of EGC in clinic.

摘要

背景/目的：miR-106b的异常表达是许多实体癌的一个特定症状。在胃癌中已观察到miR-106b的过表达。在不同的细胞培养模型中已对miR-106b对胃癌的影响进行了研究。然而，miR-106b对早期胃癌（EGC）转移的影响仍不清楚。

方法

在本研究中，采用qRT-PCR、FISH、蛋白质免疫印迹法、荧光素酶报告基因检测、迁移和侵袭检测、流式细胞术和TUNEL染色来研究miR-106b对EGC转移的影响。

结果

为了探究miR-106b在EGC中的功能，我们研究了miR-106b的下游信号传导，发现ALEX1是胃癌细胞中miR-106的直接靶标。上调ALEX1可有效挽救由miR-106b抑制剂诱导的细胞凋亡，并促进JAK1和STAT3磷酸化的表达水平。此外，过表达JAK1可减少由miR-106b抑制剂诱导的细胞凋亡，并降低胃癌细胞中凋亡蛋白的表达水平。此外，在体外和体内下调miR-106b可通过抑制JAK1/STAT3信号通路促进胃癌细胞凋亡。另外，JAK1抑制剂GLPG0643增强了miR-106b抑制剂在体内对胃癌生长的抑制作用。