Nur77 Serves as a Potential Prognostic Biomarker That Correlates with Immune Infiltration and May Act as a Good Target for Prostate adenocarcinoma

Molecules. 2023 Jan 28;28(3):1238. doi: 10.3390/molecules28031238.

Abstract

Prostate adenocarcinoma (PRAD) is the most frequent malignancy, and is the second leading cause of death due to cancer in men. Thus, new prognostic biomarkers and drug targets for PRAD are urgently needed. As we know, nuclear receptor Nur77 is important in cancer development and changes in the tumor microenvironment; whereas, the function of Nur77 in PRAD remains to be elucidated. The TCGA database was used to explore the Nur77 expression and its role in the prognosis of PRAD. It was shown that Nur77 was down regulated in PRAD, and low Nur77 expression was correlated with advanced clinical pathologic characteristics (high grade, histological type, age) and poor prognosis. Furthermore, key genes screening was examined by univariate Cox analysis and Kaplan-Meier survival. Additionally, Nur77 was closely related to immune infiltration and some anti-tumor immune functions. The differentially expressed genes (DEGs) were presented by protein-protein interaction (PPI) network analysis. Therefore, the expression level of Nur77 might help predict the survival of PRAD cases, which presents a new insight and a new target for the treatment of PRAD. In vitro experiments verified that natural product malayoside targeting Nur77 exhibited significant therapeutic effects on PRAD and largely induced cell apoptosis by up-regulating the expression of Nur77 and its mitochondrial localization. Taken together, Nur77 is a prognostic biomarker for patients with PRAD, which may refresh the profound understanding of PRAD individualized treatment.

Keywords: Nur77; prognosis; prostate cancer; target.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / genetics
  • Biomarkers
  • Humans
  • Male
  • Nuclear Receptor Subfamily 4, Group A, Member 1* / genetics
  • Prognosis
  • Prostate
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1

Grants and funding

This research was funded by Zhejiang Provincial Natural Science Foundation of China (Grant No. LGF21H280002), the Experiment Animal Science and Technology Project of Zhejiang Province (Grant No. 2016C37143), the National Natural Science Foundation of China (NSFC- 81904062), The Outstanding Youth Program of the Anhui Provincial Department of Education (2022AH020042), the Natural Science Foundation of Fujian Province of China (Grant No. 2020J01042), and the National Natural Science Foundation of China (NSFC-81673320).