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Article Abstract
Background: Transcriptome analysis of primary tumor tissues from esophageal squamous cell carcinoma (ESCC) patients with early postoperative distant metastasis identified nuclear receptor subfamily 0, group B, member 1 (NR0B1) as a novel gene associated with the malignant phenotypes of ESCC. This study aimed to elucidate the oncological functions of NR0B1 in ESCC and assess the significance of its tissue expression.
Methods: We investigated the effects of NR0B1 knockdown on the proliferation, migration, and adhesion capacities, in vivo tumor growth, and intracellular signaling pathways of ESCC cell lines. The correlation between tissue NR0B1 expression at both the mRNA and protein levels and postoperative prognosis was analyzed by using two independent cohorts.
Results: Silencing NR0B1 significantly inhibited the proliferation, migration, and adhesion capacities of ESCC cell lines and decreased tumor growth in mouse cell line derived xenograft models. Knockdown of NR0B1 results in the upregulation of cell cycle regulators p21 and p27, alongside the downregulation of TK1, cyclin E1, CDK2 and CDT1, in a manner independent of p53. Although elevated tissue NR0B1 expression did not show a significant association with TNM stage, it was identified as an independent prognostic factor at both the mRNA and protein levels across two distinct patient cohorts.
Conclusions: NR0B1 plays a critical role in the malignant phenotype of ESCC by modulating cell cycle regulators. Tissue NR0B1 expression may serve as a valuable biomarker for assessing prognostic risk in ESCC patients.
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| http://dx.doi.org/10.1245/s10434-025-17109-y | DOI Listing |
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