miR-25-3p 通过靶向 PTEN 调控 PI3K/AKT 通路抑制食管癌细胞迁移、侵袭和凋亡

MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway.

机构信息

Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province 110042, China.

Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China.

出版信息

Biosci Rep. 2020 Oct 30;40(10). doi: 10.1042/BSR20201901.

DOI:10.1042/BSR20201901

PMID:32985648

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7560540/

Abstract

BACKGROUND

Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system. MiR-25-3p was proved to be a biomarker for the diagnosis and treatment of many cancers. MiR-25-3p was found to be high expressed in the blood of EC patients. The aim of the present study was to explore the effect of miR-25-3p and its target gene on EC.

METHODS

miR-25-3p expression in the blood of EC patients and EC cells was detected by RT-qPCR. The target of miR-25-3p was identified by bioinformatics and luciferase reporter assay. After transfection, cell viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, wound healing, and transwell assays, respectively. The expressions of PTEN, Bax, Bcl-2, cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blot.

RESULTS

MiR-25-3p was high expressed in the blood of EC patients and EC cells. MiR-25-3p targeted PTEN and inhibited the expression of PTEN. MiR-25-3p mimic increased the viability, migration, invasion and the expressions of Bcl-2, and inhibited the apoptosis and the expression of Bax and cleaved caspase-3 in EC cells. MiR-25-3p mimic also enhanced the expressions of p-PI3K and p-AKT and the ratios of p-PI3K/PI3K and p-AKT/AKT in EC cells. PTEN overexpression not only had an opposite effect of miR-25-3p mimic, but also reversed the effect of miR-25-3p mimic on EC cells.

CONCLUSION

MiR-25-3p targeted PTEN to promote the migration and invasion, and inhibit apoptosis of EC cells via the PI3K/AKT pathway, which might provide a new therapeutic target for EC treatment.

摘要

背景

食管癌（EC）是消化系统最常见的恶性肿瘤之一。miR-25-3p 已被证明是许多癌症诊断和治疗的生物标志物。研究发现，miR-25-3p 在 EC 患者的血液中高表达。本研究旨在探讨 miR-25-3p 及其靶基因对 EC 的影响。

方法

采用 RT-qPCR 检测 EC 患者和 EC 细胞血液中 miR-25-3p 的表达。采用生物信息学和荧光素酶报告基因实验鉴定 miR-25-3p 的靶基因。转染后，采用 MTT、流式细胞术、划痕愈合和 Transwell 实验分别检测细胞活力、凋亡、迁移和侵袭。采用 Western blot 检测 PTEN、Bax、Bcl-2、cleaved Caspase-3、p-PI3K、PI3K、p-AKT 和 AKT 的表达。

结果

miR-25-3p 在 EC 患者和 EC 细胞的血液中高表达。miR-25-3p 靶向 PTEN 并抑制其表达。miR-25-3p 模拟物增加了 EC 细胞的活力、迁移和侵袭，同时抑制了 EC 细胞的凋亡，并下调了 Bax 和 cleaved caspase-3 的表达。miR-25-3p 模拟物还增强了 EC 细胞中 p-PI3K 和 p-AKT 的表达，以及 p-PI3K/PI3K 和 p-AKT/AKT 的比值。PTEN 过表达不仅对 miR-25-3p 模拟物具有相反的作用，而且还逆转了 miR-25-3p 模拟物对 EC 细胞的作用。