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

Abstract

Xiaobin Gu, Meilian Dong, Zheyan Liu, Jing Yang, Yonggang Shi Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of ChinaCorrespondence: Yonggang ShiDepartment of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of ChinaTel/Fax [phone]Email [email protected]: 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.Keywords: cervical cancer, epithelial–mesenchymal transition, eukaryotic translation initiation factor 4E, miR-499a-5p, radiosensitivity

Keywords

• cervical cancer
• epithelial-mesenchymal transition
• eukaryotic translation initiation factor 4e
• mir-499a-5p
• radiosensitivity;