MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway

Yunsheng Xu; Qin He; Yiyi Lu; Fengxing Tao; Liang Zhao; Rongying Ou

doi:10.1186/s12935-018-0673-1

MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway

Cancer Cell Int. 2018 Dec 4:18:198. doi: 10.1186/s12935-018-0673-1. eCollection 2018.

Authors

Yunsheng Xu^{1

2}, Qin He³, Yiyi Lu³, Fengxing Tao³, Liang Zhao¹, Rongying Ou⁴

Affiliations

¹ 1Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang China.
² 2Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen, 518107 Guangdong China.
³ 3Department of Dermatovenereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang China.
⁴ 4Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000 Zhejiang China.

Abstract

Background: We are committed to investigate miR-218-5 effects on the progression of cervical cancer (CC) cell and find out the molecular mechanism.

Methods: GSE9750 was obtained from GEO database and R Limma package was applied to filter out dysregulated genes. The pathways were enriched by GSEA software, ClusterProfiler and enrichplot packages to predict the function of DEGs. The binding sites of LYN were detected by miRanda and TargetScan. The miR2Disease database was used to find miRNAs related with CC. The expression of miR-218-5p and LYN were quantified by qRT-PCR and that of LYN protein was measured by western blot. The targeted relationships between miR-218-5p and LYN were verified by dual-luciferase reporter assay. Colony formation assays, wound healing, transwell invasion assay and flow cytometer analysis were performed to investigate the roles that miR-218-5p and LYN played in migration, invasion and death of cervical carcinoma. Xenografts established in nude mice were used to assess tumor growth in vivo.

Results: The highly expressed mRNA LYN was selected by microarray analysis in GSE9750. NF-κB signaling pathway was enriched base on GSEA results. The expression of miR-218-5p was lower but LYN was higher in CC primary tumors compared with normal control. In addition, miR-218-5p could regulate the expression of LYN in HeLa cells negatively. Overexpression of LYN could promote cell migration and invasion, but inhibit cell death in vitro, and also promote tumor formation in vivo via activating NF-κB signaling pathway which could be reversed by miR-218-5p.

Conclusions: MiR-218-5p suppressed the progression of CC via LYN/NF-κB signaling pathway.

Keywords: Cervical cancer; LYN; NF-κB signaling pathway; miR-218-5p.