NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling
Abstract Background 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. Our aims were to characterize the role of NR1B2 in KIRC. Methods...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1344-3 |
| _version_ | 1811222278235488256 |
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| author | Lei Yin Wenjia Li Guangchun Wang Heng Shi Keyi Wang Huan Yang Bo Peng |
| author_facet | Lei Yin Wenjia Li Guangchun Wang Heng Shi Keyi Wang Huan Yang Bo Peng |
| author_sort | Lei Yin |
| collection | DOAJ |
| description | Abstract Background 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. Our aims were to characterize the role of NR1B2 in KIRC. Methods NR1B2 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. Results The 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. Conclusions our results defined NR1B2 as a tumor suppressor in KIRC that restricted EMT by the LATS1/2-YAP pathway. |
| first_indexed | 2024-04-12T08:13:02Z |
| format | Article |
| id | doaj.art-1a9df6f513d0425e9b9cb3475a492bd8 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-12T08:13:02Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-1a9df6f513d0425e9b9cb3475a492bd82022-12-22T03:40:53ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-08-0138111210.1186/s13046-019-1344-3NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signalingLei Yin0Wenjia Li1Guangchun Wang2Heng Shi3Keyi Wang4Huan Yang5Bo Peng6Department of Urology, Shanghai Tenth People’s Hospital, School of Medicine in Tongji UniversityShanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan UniversityDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine in Tongji UniversityDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine in Tongji UniversityDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine in Tongji UniversityDepartment of Urology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine in Tongji UniversityAbstract Background 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. Our aims were to characterize the role of NR1B2 in KIRC. Methods NR1B2 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. Results The 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. Conclusions our results defined NR1B2 as a tumor suppressor in KIRC that restricted EMT by the LATS1/2-YAP pathway.http://link.springer.com/article/10.1186/s13046-019-1344-3NR1B2EMTLATSYAPKidney renal clear cell carcinoma |
| spellingShingle | Lei Yin Wenjia Li Guangchun Wang Heng Shi Keyi Wang Huan Yang Bo Peng NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling Journal of Experimental & Clinical Cancer Research NR1B2 EMT LATS YAP Kidney renal clear cell carcinoma |
| title | NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling |
| title_full | NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling |
| title_fullStr | NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling |
| title_full_unstemmed | NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling |
| title_short | NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling |
| title_sort | nr1b2 suppress kidney renal clear cell carcinoma kirc progression by regulation of lats 1 2 yap signaling |
| topic | NR1B2 EMT LATS YAP Kidney renal clear cell carcinoma |
| url | http://link.springer.com/article/10.1186/s13046-019-1344-3 |
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