Nur77 inhibition of β-catenin expression mediates Hepatoblastoma progression and enhances cisplatin's therapeutic effect

Nur77 抑制 β-catenin 表达介导肝母细胞瘤进展并增强顺铂的治疗效果

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作者:Jianfeng Zhou, Xingyu Liu, Hanjun Yin, Yong Zhou, Zhongya Xu, Kai Zhou, Tao Li, Yongjun Fang, Qiyang Shen

Abstract

Hepatoblastoma (HB) is the most common malignant tumor in children under 5 years old, but its pathogenesis remains unclear. Nur77 has been reported to be an important regulator for cancer progression in various cancer types. This study found that Nur77 was downregulated in HB tumors, compared with paracancer tissue. Knockout or overexpression of Nur77 in HB tumor cell line HepG2 and HuH6 could significantly enhance or inhibit the proliferation, migration and invasion of tumor cells both in vitro and in vivo. Further studies illustrated that Nur77 regulated the proliferation of tumor cells by affecting the expression of β-catenin. Nur77 agonist Csn-B effectively enhanced the therapeutic effect of cisplatin on HB tumors both in vitro and in vivo. This study confirms that Nur77 may act as an oncogene in HB tumors and mediate the progression of HB by inhibiting the expression of β-catenin, which provides a new targeted therapy for the clinical treatment of HB patients; meanwhile, the combination of Nur77 agonist and cisplatin treatment may improve the chemotherapeutic efficacy of HB patients, which provides a new idea for the improvement of the clinical prognosis of HB patients.

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