Abstract
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.
Highlights
Kidney Renal Clear Cell Carcinoma (KIRC) accounts for 75% of all renal cancers
NR1B2 associates with clinical characteristics and survival rate in the The cancer genome atlas (TCGA) database To investigate whether NR1B2 was involved in clinical KIRC progression, firstly we detected and analyzed NR1B2 expression in the TCGA database
The TCGA database showed that NR1B2 was down-regulated in various types of human cancer, such as Kidney renal papillary cell carcinoma (KIRP), bladder cancer (BLCA), breast cancer (BRCA), Head and Neck squamous cell carcinoma (HNSC), Lung adenocarcinoma (LUAD), Thyroid carcinoma (THCA) and Uterine Corpus Endometrial Carcinoma (UCEC), which further suggested that NR1B2 might play an tumor suppressor role in the progression or development of urologic and various human cancer types
Summary
Kidney 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. Yin et al Journal of Experimental & Clinical Cancer Research (2019) 38:343 inactivation of NR1B2 resulted in a lengthy delay in Wnt1-induced mammary gland tumorigenesis and a significantly slower tumor growth rate in basal-like subgroup breast cancer [8]. Liu et al [9] reported that ablation of NR1B2 in mice could suppress ErbB2-induced mammary gland tumorigenesis, which suggested NR1B2 might be a tumor promotor to drive cancer cell growth and metastasis. All these results strongly indicated that NR1B2 played a pivotal role in cancer development. Little knowledge is known regarding to its expression and biological role in KIRC
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