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Background <p>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 <i>NR0B1</i> in ESCC and assess the significance of its tissue expression.</p> Methods <p>We investigated the effects of <i>NR0B1</i> knockdown on the proliferation, migration, and adhesion capacities, in vivo tumor growth, and intracellular signaling pathways of ESCC cell lines. The correlation between tissue <i>NR0B1</i> expression at both the mRNA and protein levels and postoperative prognosis was analyzed by using two independent cohorts.</p> Results <p>Silencing <i>NR0B1</i> 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 <i>NR0B1</i> 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<i>.</i> Although elevated tissue <i>NR0B1</i> 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.</p> Conclusions <p><i>NR0B1</i> plays a critical role in the malignant phenotype of ESCC by modulating cell cycle regulators. Tissue <i>NR0B1</i> expression may serve as a valuable biomarker for assessing prognostic risk in ESCC patients.</p>

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Association of NR0B1 with Malignant Phenotypes in Esophageal Squamous Cell Carcinoma Through Modulation of p53-Independent Cell-Cycle Regulation

  • 期刊论文

  • 发表日期：

    2025年3月13日

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  • Akimitsu Iizuka,
  • Mitsuro Kanda,
  • Yusuke Sato,
  • Dai Shimizu,
  • Shinichi Umeda,
  • Haruyoshi Tanaka,
  • Norifumi Hattori,
  • Masamichi Hayashi,
  • Chie Tanaka,
  • Yasuhiro Kodera

摘要

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.