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Nuclear receptor subfamily 3 group c member 2 (NR3C2) is downregulated due to hypermethylation and plays a tumor-suppressive role in colon cancer

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Abstract

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.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Author notes

  1. Xianzhe Li and Aimin Yang are Co-first authors.

Authors and Affiliations

  1. Department of General Surgery, Nanshi Hospital of Nanyang, Nanyang, 473000, China

    Xianzhe Li & Hengwei Shi

  2. Department of Radiotherapy, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an Second People’s Hospital, Huai’an, 223002, China

    Aimin Yang

  3. Department of Medical Oncology, Nanshi Hospital of Nanyang, Nanyang, 473000, China

    Penghao Wen & Zhenghong Xiao

  4. Department of Radiotherapy, Nanshi Hospital of Nanyang, Nanyang, 473000, China

    Yan Yuan

  5. Department of Pediatric Surgery, Huai’an Women and Children’s Hospital, 104 Renmin South Road, Huai’an, 223001, China

    Ren Wang

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  1. Xianzhe Li
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  4. Yan Yuan
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Contributions

XL and AY: conducted the experiments and wrote the paper. PW, YY, and ZX: analyzed the data and contributed to bioinformatics. HS: contributed to bioinformatics and supervised the study. RW: contributed to the concept and design. All authors read and approved the final manuscript.

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Correspondence to Ren Wang.

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Li, X., Yang, A., Wen, P. et al. Nuclear receptor subfamily 3 group c member 2 (NR3C2) is downregulated due to hypermethylation and plays a tumor-suppressive role in colon cancer. Mol Cell Biochem 477, 2669–2679 (2022). https://doi.org/10.1007/s11010-022-04449-6

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  • DOI: https://doi.org/10.1007/s11010-022-04449-6

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