白藜芦醇通过miR-937/FOXQ1信号通路抑制视网膜母细胞瘤细胞增殖

doi:10.12092/j.issn.1009-2501.2020.02.009

中国临床药理学与治疗学 ›› 2020, Vol. 25 ›› Issue (2): 174-181.doi: 10.12092/j.issn.1009-2501.2020.02.009

白藜芦醇通过miR-937/FOXQ1信号通路抑制视网膜母细胞瘤细胞增殖

宋慧，王英豪

恩施土家族苗族自治州中心医院眼科中心，恩施 445000，湖北

收稿日期:2019-09-27 修回日期:2020-02-13 出版日期:2020-02-26 发布日期:2020-03-06
通讯作者: 王英豪，男，本科，主治医师，研究方向：视网膜母细胞瘤防治。 Tel: 13907268600 E-mail: w050350813@163.com
作者简介:宋慧，女，本科，主治医师，研究方向：眼底病，视网膜母细胞瘤防治。 E-mail: 702072251@qq.com
基金资助:
恩施州科技计划项目（E20180013）

Resveratrol inhibits the proliferation of retinoblastoma cells via miR-937/FOXQ1 pathway

SONG Hui, WANG Yinghao

Eye Center of the Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, Hubei, China

Received:2019-09-27 Revised:2020-02-13 Online:2020-02-26 Published:2020-03-06

摘要/Abstract

摘要： 目的:研究白藜芦醇（RES）对视网膜母细胞瘤Y79细胞增殖的影响及其可能的作用机制。方法:CCK-8方法和流式细胞术分析细胞增殖和凋亡情况；TargetScan软件预测miR-937与叉头框蛋白Q1（FOXQ1）之间的关系，并采用双荧光素酶报告基因系统检测它们之间的相互作用；miR-937和FOXQ1 mRNA和蛋白表达水平分别采用逆转录-定量聚合酶链反应法（RT-qPCR）和Western blot法检测。结果:RES抑制Y79细胞增殖，诱导其凋亡；视网膜母细胞瘤细胞系中miR-937表达水平较正常组织明显降低，而RES可明显诱导Y79细胞中miR-937表达；FOXQ1可以与miR-937直接相互作用，且其表达水平与miR-937呈负相关性；视网膜母细胞瘤细胞系中FOXQ1表达水平较正常细胞明显增高，而RES可明显抑制Y79细胞中FOXQ1表达；与RES单纯处理组相比，RES+miR-937 inhibitor组明显降低miR-937表达，促使了FOXQ1表达，诱导Y79细胞增殖，并降低其凋亡。结论:RES通过上调miR-937水平降低FOXQ1表达，进而抑制视网膜母细胞瘤细胞增殖、诱导其凋亡，提示miR-937/FOXQ1信号通路可能是视网膜母细胞瘤治疗的新靶标。

关键词: 白藜芦醇, 视网膜母细胞瘤, 增殖, miR-937/FOXQ1信号通路

Abstract: AIM: To study the impact of resveratrol (RES) on the proliferation of retinoblastoma in vitro, and to explore its possible mechanism. METHODS:CCK-8 assay and flow cytometry assay were used to measure cell viability and apoptosis. The relationship between miR-937 and forkhead box Q1 (FOXQ1) was predicted and confirmed by TargetScan and dual-luciferase reporter assay. In addition, gene and protein expression was detected using reverse transcription-quantitative polymerase chain reaction (RT-PCR) and Western blot, respectively. RESULTS:RES inhibited the proliferation and induced the apoptosis of Y79 cells with time- and concentration-dependent manner. miR-937 was found to be down-regulated in retinoblastoma cell lines; treatment with RES increased the expression of miR-937 in Y79 cells. FOXQ1 was identified as a direct target of miR-937, and its expression was negatively associated with that of miR-937. Additionally, FOXQ1 was up-regulated in retinoblastoma cell lines; treatment with RES decreased the expression of FOXQ1 in Y79 cells. Furthermore, compared with treatment with RES alone, the combination of transfection with miR-937 inhibitor and RES treatment significantly decreased the expression of miR-937, increased FOXQ1 expression, promoted Y79 cell proliferation and reduced the apoptosis of cells in vitro. CONCLUSION: RES reduced the proliferation and induced the apoptosis of retinoblastoma cells by decreasing FOXQ1 expression via the up-regulation of miR-937, suggesting that the miR-937/FOXQ1 signaling pathway may be a novel therapeutic target in the treatment of retinoblastoma.

Key words: resveratrol, retinoblastoma, proliferation, miR-937/FOXQ1 signaling pathway

中图分类号:

R965.2
R774

宋慧，王英豪. 白藜芦醇通过miR-937/FOXQ1信号通路抑制视网膜母细胞瘤细胞增殖[J]. 中国临床药理学与治疗学, 2020, 25(2): 174-181.

SONG Hui, WANG Yinghao. Resveratrol inhibits the proliferation of retinoblastoma cells via miR-937/FOXQ1 pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(2): 174-181.

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白藜芦醇通过miR-937/FOXQ1信号通路抑制视网膜母细胞瘤细胞增殖

Resveratrol inhibits the proliferation of retinoblastoma cells via miR-937/FOXQ1 pathway

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