PMID- 35425712 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220429 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 12 DP - 2022 TI - BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells. PG - 852515 LID - 10.3389/fonc.2022.852515 [doi] LID - 852515 AB - BACKGROUND: BAP1 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. METHODS: Raw 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. RESULTS: Nuclear 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. CONCLUSIONS: In 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. CI - Copyright (c) 2022 Liu, Xu, Li, Yu, Feng, Xu and Chen. FAU - Liu, Rui-Ji AU - Liu RJ AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. FAU - Xu, Zhi-Peng AU - Xu ZP AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. FAU - Li, Shu-Ying AU - Li SY AD - Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital affiliate to School of Medicine, UESTC, Chengdu, China. FAU - Yu, Jun-Jie AU - Yu JJ AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. FAU - Feng, Ning-Han AU - Feng NH AD - Department of Urology, Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Xu, Bin AU - Xu B AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. FAU - Chen, Ming AU - Chen M AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. AD - Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China. LA - eng PT - Journal Article DEP - 20220329 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC9004599 OTO - NOTNLM OT - DNA methylation OT - ceRNA OT - clear-cell renal cell carcinoma OT - immune microenvironment OT - prognosis COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/04/16 06:00 MHDA- 2022/04/16 06:01 PMCR- 2022/01/01 CRDT- 2022/04/15 05:31 PHST- 2022/01/11 00:00 [received] PHST- 2022/02/25 00:00 [accepted] PHST- 2022/04/15 05:31 [entrez] PHST- 2022/04/16 06:00 [pubmed] PHST- 2022/04/16 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2022.852515 [doi] PST - epublish SO - Front Oncol. 2022 Mar 29;12:852515. doi: 10.3389/fonc.2022.852515. eCollection 2022.