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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Frontiers Media S.A.
2022-03-01
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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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issn | 2234-943X |
language | English |
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publishDate | 2022-03-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Oncology |
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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