BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells

BackgroundBAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, thi...

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Main Authors: Rui-ji Liu, Zhi-Peng Xu, Shu-Ying Li, Jun-Jie Yu, Ning-han Feng, Bin Xu, Ming Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.852515/full
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author Rui-ji Liu
Rui-ji Liu
Zhi-Peng Xu
Zhi-Peng Xu
Shu-Ying Li
Jun-Jie Yu
Jun-Jie Yu
Ning-han Feng
Bin Xu
Bin Xu
Ming Chen
Ming Chen
Ming Chen
author_facet Rui-ji Liu
Rui-ji Liu
Zhi-Peng Xu
Zhi-Peng Xu
Shu-Ying Li
Jun-Jie Yu
Jun-Jie Yu
Ning-han Feng
Bin Xu
Bin Xu
Ming Chen
Ming Chen
Ming Chen
author_sort Rui-ji Liu
collection DOAJ
description BackgroundBAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC.MethodsRaw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence in situ hybridization (FISH) assays were used to confirm the ceRNA network.ResultsNuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels.ConclusionsIn BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.
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spelling doaj.art-18e467af63984a37abef4f805ce21d7e2022-12-21T23:53:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-03-011210.3389/fonc.2022.852515852515BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer CellsRui-ji Liu0Rui-ji Liu1Zhi-Peng Xu2Zhi-Peng Xu3Shu-Ying Li4Jun-Jie Yu5Jun-Jie Yu6Ning-han Feng7Bin Xu8Bin Xu9Ming Chen10Ming Chen11Ming Chen12Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaSurgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, ChinaDepartment of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaSurgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, ChinaSichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital affiliate to School of Medicine, UESTC, Chengdu, ChinaDepartment of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaSurgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, ChinaDepartment of Urology, Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaSurgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, ChinaDepartment of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaSurgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, ChinaNanjing Lishui District People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, ChinaBackgroundBAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC.MethodsRaw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence in situ hybridization (FISH) assays were used to confirm the ceRNA network.ResultsNuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels.ConclusionsIn BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.https://www.frontiersin.org/articles/10.3389/fonc.2022.852515/fullceRNADNA methylationimmune microenvironmentclear-cell renal cell carcinomaprognosis
spellingShingle Rui-ji Liu
Rui-ji Liu
Zhi-Peng Xu
Zhi-Peng Xu
Shu-Ying Li
Jun-Jie Yu
Jun-Jie Yu
Ning-han Feng
Bin Xu
Bin Xu
Ming Chen
Ming Chen
Ming Chen
BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells
Frontiers in Oncology
ceRNA
DNA methylation
immune microenvironment
clear-cell renal cell carcinoma
prognosis
title BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells
title_full BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells
title_fullStr BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells
title_full_unstemmed BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells
title_short BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells
title_sort bap1 related cerna neat1 mir 10a 5p serpine1 promotes proliferation and migration of kidney cancer cells
topic ceRNA
DNA methylation
immune microenvironment
clear-cell renal cell carcinoma
prognosis
url https://www.frontiersin.org/articles/10.3389/fonc.2022.852515/full
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