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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BMC
2018-12-01
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Series: | Cancer Cell International |
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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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issn | 1475-2867 |
language | English |
last_indexed | 2024-12-22T15:03:14Z |
publishDate | 2018-12-01 |
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series | Cancer Cell International |
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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