Department of General Surgery, Nanshi Hospital of Nanyang, Nanyang, 473000, China.
Department of Radiotherapy, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital, Huai'an, 223002, China.
Mol Cell Biochem. 2022 Nov;477(11):2669-2679. doi: 10.1007/s11010-022-04449-6. Epub 2022 May 23.
Nuclear receptor subfamily 3 group c member 2 (NR3C2) has been reported to function as a tumor suppressor in several tumors. However, the clinical significance and potential action mechanisms of NR3C2 in colon cancer (COAD) remain unclear. NR3C2 expression and its correlation with clinicopathological features in COAD were analyzed based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic (ROC) curves and Human Protein Atlas (HPA) database were used to evaluate the diagnostic and prognostic values of NR3C2 in COAD. Immune infiltration and DNA methylation analyses were performed by Gene Set Cancer Analysis (GSCA) database. NR3C2-correlated genes were identified by UALCAN database and subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses. Cell apoptosis and proliferation were evaluated using TUNEL and CCK-8 assays, respectively. NR3C2 was downregulated in COAD based on TCGA and GEO databases, which may be due to promoter hypermethylation. NR3C2 expression was correlated with prognosis and immune infiltration of COAD. High NR3C2 expression displayed good diagnostic value in COAD. KEGG pathway analysis presented that NR3C2-correlated genes were mainly clustered in choline metabolism in cancer and apoptosis. In vitro experiments confirmed that NR3C2 overexpression induced apoptosis and suppressed proliferation in COAD cells. In conclusion, our study revealed the potential prognostic and diagnostic values of NR3C2 and provided insights into understanding the tumor-suppressive role of NR3C2 in COAD progression.
核受体亚家族 3 组 C 成员 2（NR3C2）已被报道在几种肿瘤中作为肿瘤抑制因子发挥作用。然而，NR3C2 在结肠癌（COAD）中的临床意义和潜在作用机制仍不清楚。本研究基于癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据库，分析了 NR3C2 在 COAD 中的表达及其与临床病理特征的相关性。接收器操作特征（ROC）曲线和人类蛋白质图谱（HPA）数据库用于评估 NR3C2 在 COAD 中的诊断和预后价值。通过基因集癌症分析（GSCA）数据库进行免疫浸润和 DNA 甲基化分析。通过 UALCAN 数据库鉴定 NR3C2 相关基因，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集途径分析。采用 TUNEL 和 CCK-8 检测分别评估细胞凋亡和增殖。基于 TCGA 和 GEO 数据库，发现 NR3C2 在 COAD 中下调，这可能是由于启动子超甲基化所致。NR3C2 的表达与 COAD 的预后和免疫浸润相关。高 NR3C2 表达在 COAD 中具有良好的诊断价值。KEGG 通路分析表明，NR3C2 相关基因主要聚类在癌症中的胆碱代谢和细胞凋亡。体外实验证实，NR3C2 过表达可诱导 COAD 细胞凋亡并抑制增殖。综上所述，本研究揭示了 NR3C2 的潜在预后和诊断价值，并深入了解了 NR3C2 在 COAD 进展中的肿瘤抑制作用。
