NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling
NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling
复制标题
NR1B2 通过调节 LATS 1/2-YAP 信号传导抑制肾透明细胞癌 (KIRC) 进展
DOI：
10.1186/s13046-019-1344-3
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发表时间：
2019-08-07
影响因子：
11.3
通讯作者：
Peng, Bo
中科院分区：
文献类型：
--
作者：
Yin, Lei;Li, Wenjia;Peng, Bo
肾透明细胞癌（KIRC）占所有肾癌的75%。先前的研究对NR 1B 2在癌症中的作用存在矛盾的证据，并且其在KIRC中的表达和生物学作用仍不清楚。目的研究NR 1B 2在KIRC中的作用。采用RT-PCR、western blot和组织芯片（TMA）检测临床KIRC标本。分析NR 1B 2表达与临床特征的关系。KIRC细胞系稳定过表达NR 1B 2或使用慢病毒系统敲低NR 1B 2。通过迁移和侵袭试验分析细胞，然后注射到裸鼠体内以评估肿瘤生长和转移。结果NR 1B 2在KIRC中的表达在TCGA数据库和我们的临床标本中均显著下调。此外，NR 1B 2表达与肿瘤分期呈负相关，与总生存率和无病生存率呈正相关。单因素和多因素分析表明，NR 1B 2表达水平可作为KIRC预后的独立预测因素。NR 1B 2过表达可显著抑制KIRC细胞的侵袭和转移，而敲低NR 1B 2可显著促进KIRC细胞的侵袭和转移。结论NR 1B 2可能是通过LATS 1/2-雅普通路抑制KIRC EMT的抑癌基因。
BackgroundKidney Renal Clear Cell Carcinoma (KIRC) accounts for 75% of all renal cancers. Previous study had conflict evidences regarding NR1B2 role in cancer, and its expression and biological role in KIRC remained unclear. Our aims were to characterize the role of NR1B2 in KIRC.MethodsNR1B2 expression in TCGA database were analyzed. Clinical KIRC samples were examined by RT-PCR, western blot and tissue microarray (TMA). The relationship between NR1B2 expression and the clinical characteristics were evaluated. KIRC cell line were stably overexpressed NR1B2 or with an NR1B2 knocked down using lentivirus system. The cells were analyzed by migration and invasion assay, then injected into nude mice to assess tumor growth and metastasis. EMT marker expression and LATS 1/2-YAP pathway demonstration were detected by the TCGA database and western blot.ResultsThe expression of NR1B2 in KIRC was significantly down-regulated in the TCGA database and our clinical samples. Moreover, NR1B2 expression negatively correlated with tumor stage and positively correlated with overall and disease-free survival rate. Univariate and multivariate analyses indicated the expression level of NR1B2 could be used as an independent factor for predicting the prognosis of KIRC. Overexpression NR1B2 significantly inhibited and knockdown NR1B2 markedly promoted KIRC cell invasion and metastasis both in vitro and in vivo. Mechanistic investigations revealed that NR1B2 might be a tumor suppressor to inhibit EMT through the LATS1/2-YAP pathway.Conclusionsour results defined NR1B2 as a tumor suppressor in KIRC that restricted EMT by the LATS1/2-YAP pathway.