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微小RNA-499a-5p通过靶向真核生物翻译起始因子4E抑制宫颈癌细胞的增殖、侵袭、迁移和上皮-间质转化，并增强其放射敏感性。

MiR-499a-5p Inhibits Proliferation, Invasion, Migration, and Epithelial-Mesenchymal Transition, and Enhances Radiosensitivity of Cervical Cancer Cells via Targeting eIF4E.

作者信息

Gu Xiaobin, Dong Meilian, Liu Zheyan, Yang Jing, Shi Yonggang

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Apr 5;13:2913-2924. doi: 10.2147/OTT.S241631. eCollection 2020.

DOI:10.2147/OTT.S241631
PMID:32308424
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7148431/
Abstract

INTRODUCTION

The present study aimed to explore the role of miR-499a-5p and its molecular mechanism in cervical cancer (CC).

METHODS

Quantitative real-time PCR (QRT-PCR) and Western blotting were performed to detect the expression of miR-499a-5p and eukaryotic translation initiation factor 4E (eIF4E) in CC tissues and cell lines. The proliferation, migration, and invasion of CC cells were detected by MTT assay, wound healing assay, and Transwell assay. Apoptosis was evaluated by flow cytometry and alterations of apoptosis-related genes. The effect of miR-499a-5p on epithelial-mesenchymal transition (EMT) was examined by determining the protein levels of EMT-associated genes. Then, colony formation assay was used to determine the radiosensitivity of CC cells. A dual-luciferase reporter assay was performed to confirm the direct target of miR-499a-5p.

RESULTS

MiR-499a-5p was significantly downregulated in CC tissues and cell lines. Overexpression of miR-499a-5p or eIF4E knockdown markedly inhibited cell proliferation, invasion, migration, and EMT, and enhanced apoptosis. eIF4E was predicted and verified as a target gene of miR-499a-5p. The influence of miR-499a-5p upregulation on proliferation, apoptosis, invasion, migration, EMT, and radiosensitivity was abrogated by eIF4E overexpression.

DISCUSSION

MiR-499a-5p promoted the apoptosis and radiosensitivity and inhibited proliferation, invasion, migration, and EMT by directly targeting eIF4E in CC cells.

摘要

引言

本研究旨在探讨miR-499a-5p在宫颈癌（CC）中的作用及其分子机制。

方法

采用定量实时PCR（QRT-PCR）和蛋白质印迹法检测CC组织及细胞系中miR-499a-5p和真核翻译起始因子4E（eIF4E）的表达。通过MTT法、伤口愈合试验和Transwell试验检测CC细胞的增殖、迁移和侵袭能力。采用流式细胞术及凋亡相关基因的改变评估细胞凋亡情况。通过检测上皮-间质转化（EMT）相关基因的蛋白水平，研究miR-499a-5p对EMT的影响。然后，采用集落形成试验确定CC细胞的放射敏感性。进行双荧光素酶报告基因试验以确认miR-499a-5p的直接靶标。

结果

miR-499a-5p在CC组织和细胞系中显著下调。miR-499a-5p过表达或eIF4E敲低显著抑制细胞增殖、侵袭、迁移和EMT，并增强细胞凋亡。eIF4E被预测并验证为miR-499a-5p的靶基因。eIF4E过表达消除了miR-499a-5p上调对增殖、凋亡、侵袭、迁移、EMT和放射敏感性的影响。

讨论

miR-499a-5p通过直接靶向CC细胞中的eIF4E促进细胞凋亡和放射敏感性，并抑制细胞增殖、侵袭、迁移和EMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acee/7148431/9f94ee7f487a/OTT-13-2913-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acee/7148431/9411879612f6/OTT-13-2913-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acee/7148431/9f94ee7f487a/OTT-13-2913-g0007.jpg

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