CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells

Lili Bai,* Wangjie Sun,* Zhe Han, Hua Tang Tianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin,...

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Main Authors: Bai L, Sun W, Han Z, Tang H
Format: Article
Language:English
Published: Dove Medical Press 2021-01-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/circsnd1-regulated-by-tnf-alpha-promotes-the-migration-and-invasion-of-peer-reviewed-article-CMAR
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author Bai L
Sun W
Han Z
Tang H
author_facet Bai L
Sun W
Han Z
Tang H
author_sort Bai L
collection DOAJ
description Lili Bai,* Wangjie Sun,* Zhe Han, Hua Tang Tianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua TangTianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin 300070, People’s Republic of ChinaTel/Fax +86 22 23542503Email tangh@tmu.edu.cnAim: To explore the role and potential mechanism of circSND1 in cervical cancer (CC).Main Methods: qRT-PCR was used to determine the expression of circSND1 in tumor necrosis factor-α (TNF-α)-treated HeLa cells. CircSND1 overexpression and knockdown were performed to indicate the functional role of circSND1 in vitro and in vivo. Luciferase assay was used to analyze promoter activity. The expression and regulation of circSND1, miR-125a-3p and FUT6 were evaluated using EGFP fluorescent reporter assay and rescue experiments. Immunofluorescence and Western blot assays were used to analyze the activation of nuclear factor-κB (NF-κB).Results: In HeLa cells, TNF-α up-regulated the expression of circSND1 by activating the NF-κB signaling pathway. Overexpression of circSND1 significantly increased the migration and invasion and the epithelial–mesenchymal transition (EMT) process of CC cells, and promoted tumor metastasis in xenograft nude mouse model, whereas down-regulation of circSND1 exerted opposite effects. Furthermore, circSND1 enhanced the expression of FUT6 via sponging miR-125a-3p, and FUT6 activated NF-κB signaling pathway.Conclusion: We found that circSND1 promoted the expression of FUT6 and the malignant behavior of cervical cancer through the ceRNA mechanism, and there was a TNF-α/NF-κB/circSND1/miR-125a-3p/FUT6/NF-κB positive feedback pathway between them, which suggests that circSND1 can be a promising prognostic marker and therapeutical target for cervical cancer.Keywords: circSND1, miR-125a-3p, FUT6, NF-κB, ceRNA, cervical cancer
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spelling doaj.art-45db2e7a569e4a3cb25e0303ecc752ce2022-12-21T22:00:54ZengDove Medical PressCancer Management and Research1179-13222021-01-01Volume 1325927561089CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer CellsBai LSun WHan ZTang HLili Bai,* Wangjie Sun,* Zhe Han, Hua Tang Tianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua TangTianjin Life Science Research Center, Tianjin Key Laboratory of Inflammation Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin 300070, People’s Republic of ChinaTel/Fax +86 22 23542503Email tangh@tmu.edu.cnAim: To explore the role and potential mechanism of circSND1 in cervical cancer (CC).Main Methods: qRT-PCR was used to determine the expression of circSND1 in tumor necrosis factor-α (TNF-α)-treated HeLa cells. CircSND1 overexpression and knockdown were performed to indicate the functional role of circSND1 in vitro and in vivo. Luciferase assay was used to analyze promoter activity. The expression and regulation of circSND1, miR-125a-3p and FUT6 were evaluated using EGFP fluorescent reporter assay and rescue experiments. Immunofluorescence and Western blot assays were used to analyze the activation of nuclear factor-κB (NF-κB).Results: In HeLa cells, TNF-α up-regulated the expression of circSND1 by activating the NF-κB signaling pathway. Overexpression of circSND1 significantly increased the migration and invasion and the epithelial–mesenchymal transition (EMT) process of CC cells, and promoted tumor metastasis in xenograft nude mouse model, whereas down-regulation of circSND1 exerted opposite effects. Furthermore, circSND1 enhanced the expression of FUT6 via sponging miR-125a-3p, and FUT6 activated NF-κB signaling pathway.Conclusion: We found that circSND1 promoted the expression of FUT6 and the malignant behavior of cervical cancer through the ceRNA mechanism, and there was a TNF-α/NF-κB/circSND1/miR-125a-3p/FUT6/NF-κB positive feedback pathway between them, which suggests that circSND1 can be a promising prognostic marker and therapeutical target for cervical cancer.Keywords: circSND1, miR-125a-3p, FUT6, NF-κB, ceRNA, cervical cancerhttps://www.dovepress.com/circsnd1-regulated-by-tnf-alpha-promotes-the-migration-and-invasion-of-peer-reviewed-article-CMARcircsnd1mir-125a-3pfut6nf-κbcernacervical cancer
spellingShingle Bai L
Sun W
Han Z
Tang H
CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells
Cancer Management and Research
circsnd1
mir-125a-3p
fut6
nf-κb
cerna
cervical cancer
title CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells
title_full CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells
title_fullStr CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells
title_full_unstemmed CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells
title_short CircSND1 Regulated by TNF-α Promotes the Migration and Invasion of Cervical Cancer Cells
title_sort circsnd1 regulated by tnf alpha promotes the migration and invasion of cervical cancer cells
topic circsnd1
mir-125a-3p
fut6
nf-κb
cerna
cervical cancer
url https://www.dovepress.com/circsnd1-regulated-by-tnf-alpha-promotes-the-migration-and-invasion-of-peer-reviewed-article-CMAR
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