NDLI: Clinical significance and oncogenic function of NR1H4 in clear cell renal cell carcinoma

Content Provider	Springer Nature : BioMed Central
Author	Huang, Shiyu Hou, Yanguang Hu, Min Hu, Juncheng Liu, Xiuheng
Abstract	Background Nuclear receptor subfamily 1 group H member 4 (NR1H4) have been reported in various cancer types, however, little is known about the clinical values and biological function in clear cell Renal cell carcinoma (ccRCC). Methods The expression pattens of NR1H4 in ccRCC were investigated in clinical specimens, cell lines and publicly‑available databases. Cell Counting Kit-8 (CCK-8), colony formation, 5-ethynyl-2' -deoxyuridine (EdU), transwell and cell wound healing assays were performed to assess the biological functions of NR1H4 in 786-O ccRCC cells. Gene set enrichment analysis (GSEA), Flow Cytometry, quantitative real‐time PCR (qRT-PCR), western blot and immunofluorescence were performed to explore the molecular mechanism of NR1H4 in ccRCC. We explored the early diagnostic value, prognostic value, genetic mutation and DNA methylation of NR1H4 by a comprehensive bioinformatics analysis based on the data published in the following databases: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Kaplan‐Meier Plotter, Gene Expression Profiling Interactive Analysis (GEPIA), UNIVERSITY OF CALIFORNIA SANTA CRUZ Xena (UCSC Xena), cBio Cancer Genomics Portal, MethSurv, SurvivalMeth and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). Its correlation with tumor-infiltrating immune cells in ccRCC was analyzed by Tumor Immune Estimation Resource 2.0 (TIMER2.0) and Tumor Immune System Interactions Database (TISIDB). Results In this study, NR1H4 was found to be highly expressed in ccRCC tissues and ccRCC cell lines. Knockdown of NR1H4 significantly suppressed cancer cell proliferation, migration and invasion. Mechanistically, tumor‐associated signaling pathways were enriched in the NR1H4 overexpression group and si-NR1H4 could induce the downregulation of Cyclin E2 (CCNE2). By bioinformatics analysis, NR1H4 was identified as highly expressed in stage I ccRCC with a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.8). Genetic alteration and DNA methylation of NR1H4 were significantly associated with prognosis in ccRCC patients. Moreover, NR1H4 expression associated with immune cell infiltration levels in ccRCC, which provides a new idea for immunotherapy. Conclusions Our study indicated that NR1H4 might be a potential tumor biomarker and therapeutic target for ccRCC which could promote cancer cell proliferation, migration and invasion via regulating CCNE2.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-10087-4.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-022-10087-4
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-09-19
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health NR1H4 ccRCC Malignant phenotype CCNE2 Diagnosis Prognosis Multi-omics Immunotherapy Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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