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

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 G...

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Main Authors: Yunsheng Xu, Qin He, Yiyi Lu, Fengxing Tao, Liang Zhao, Rongying Ou
Format: Article
Language:English
Published: BMC 2018-12-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-018-0673-1
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author Yunsheng Xu
Qin He
Yiyi Lu
Fengxing Tao
Liang Zhao
Rongying Ou
author_facet Yunsheng Xu
Qin He
Yiyi Lu
Fengxing Tao
Liang Zhao
Rongying Ou
author_sort Yunsheng Xu
collection DOAJ
description 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.
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spelling doaj.art-c97addd51b7142219dc7a190b78dbb082022-12-21T18:22:03ZengBMCCancer Cell International1475-28672018-12-0118111510.1186/s12935-018-0673-1MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathwayYunsheng Xu0Qin He1Yiyi Lu2Fengxing Tao3Liang Zhao4Rongying Ou5Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatovenereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatovenereology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Dermatovenereology, The First Affiliated Hospital of Wenzhou Medical UniversityLaboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12935-018-0673-1Cervical cancermiR-218-5pLYNNF-κB signaling pathway
spellingShingle Yunsheng Xu
Qin He
Yiyi Lu
Fengxing Tao
Liang Zhao
Rongying Ou
MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway
Cancer Cell International
Cervical cancer
miR-218-5p
LYN
NF-κB signaling pathway
title MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway
title_full MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway
title_fullStr MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway
title_full_unstemmed MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway
title_short MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway
title_sort microrna 218 5p inhibits cell growth and metastasis in cervical cancer via lyn nf κb signaling pathway
topic Cervical cancer
miR-218-5p
LYN
NF-κB signaling pathway
url http://link.springer.com/article/10.1186/s12935-018-0673-1
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