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CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma
Dysregulation of C-Type Lectin Domain Family 3 Member B (CLEC3B) in serum or tumor tissues has been reported in patients with various cancer types. However, the expression and function of CLEC3B in clear cell renal cell carcinoma (ccRCC) remain unknown. To examine the function of CLEC3B in ccRCC, Th...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111577/ https://www.ncbi.nlm.nih.gov/pubmed/30066941 http://dx.doi.org/10.3892/or.2018.6590 |
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author | Liu, Jian Liu, Zhe Liu, Qun Li, Lina Fan, Xiaona Wen, Tao An, Guangyu |
author_facet | Liu, Jian Liu, Zhe Liu, Qun Li, Lina Fan, Xiaona Wen, Tao An, Guangyu |
author_sort | Liu, Jian |
collection | PubMed |
description | Dysregulation of C-Type Lectin Domain Family 3 Member B (CLEC3B) in serum or tumor tissues has been reported in patients with various cancer types. However, the expression and function of CLEC3B in clear cell renal cell carcinoma (ccRCC) remain unknown. To examine the function of CLEC3B in ccRCC, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were examined to determine the expression of CLEC3B at the transcriptional level and it was demonstrated that CLEC3B mRNA was significantly downregulated in ccRCC compared with normal tissues (P<0.0001 and P=0.0392 in TCGA and GEO databases, respectively). The downregulation of CLEC3B was further validated at the protein level in 78.9% of ccRCCs by immunohistochemistry. To investigate the potential genetic mechanism for CLEC3B downregulation in ccRCC, copy number analysis was performed by profiling the copy number variation data from the TCGA project and it was revealed that the copy number loss of CLEC3B was prevalent in up to 88.1% of patients with ccRCC. CLEC3B genetic deletion was coupled with the well-known genetic loss of the von Hippel-Lindau tumor suppressor, which is a characteristic oncogenic event during ccRCC carcinogenesis. The downregulation of CLEC3B was associated with tumor progression and predicted unfavorable prognostic outcomes in the TCGA cohort. Real-time cell analyzer system technology revealed that CLEC3B inhibited the proliferation of ccRCC cell lines in vitro and that the mitogen-activated protein kinase pathway may contribute to this process. CLEC3B demonstrated substantial positive associations with proliferation inhibitors, but inverse associations with proliferation inducers and markers in two large ccRCC cohorts, suggesting that CLEC3B was able to identify ccRCCs with a lower proliferation capacity. In conclusion, the results of the present study propose that CLEC3B is a promising target for therapeutic intervention in ccRCC. |
format | Online Article Text |
id | pubmed-6111577 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-61115772018-08-30 CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma Liu, Jian Liu, Zhe Liu, Qun Li, Lina Fan, Xiaona Wen, Tao An, Guangyu Oncol Rep Articles Dysregulation of C-Type Lectin Domain Family 3 Member B (CLEC3B) in serum or tumor tissues has been reported in patients with various cancer types. However, the expression and function of CLEC3B in clear cell renal cell carcinoma (ccRCC) remain unknown. To examine the function of CLEC3B in ccRCC, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were examined to determine the expression of CLEC3B at the transcriptional level and it was demonstrated that CLEC3B mRNA was significantly downregulated in ccRCC compared with normal tissues (P<0.0001 and P=0.0392 in TCGA and GEO databases, respectively). The downregulation of CLEC3B was further validated at the protein level in 78.9% of ccRCCs by immunohistochemistry. To investigate the potential genetic mechanism for CLEC3B downregulation in ccRCC, copy number analysis was performed by profiling the copy number variation data from the TCGA project and it was revealed that the copy number loss of CLEC3B was prevalent in up to 88.1% of patients with ccRCC. CLEC3B genetic deletion was coupled with the well-known genetic loss of the von Hippel-Lindau tumor suppressor, which is a characteristic oncogenic event during ccRCC carcinogenesis. The downregulation of CLEC3B was associated with tumor progression and predicted unfavorable prognostic outcomes in the TCGA cohort. Real-time cell analyzer system technology revealed that CLEC3B inhibited the proliferation of ccRCC cell lines in vitro and that the mitogen-activated protein kinase pathway may contribute to this process. CLEC3B demonstrated substantial positive associations with proliferation inhibitors, but inverse associations with proliferation inducers and markers in two large ccRCC cohorts, suggesting that CLEC3B was able to identify ccRCCs with a lower proliferation capacity. In conclusion, the results of the present study propose that CLEC3B is a promising target for therapeutic intervention in ccRCC. D.A. Spandidos 2018-10 2018-07-23 /pmc/articles/PMC6111577/ /pubmed/30066941 http://dx.doi.org/10.3892/or.2018.6590 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Liu, Jian Liu, Zhe Liu, Qun Li, Lina Fan, Xiaona Wen, Tao An, Guangyu CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma |
title | CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma |
title_full | CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma |
title_fullStr | CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma |
title_full_unstemmed | CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma |
title_short | CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma |
title_sort | clec3b is downregulated and inhibits proliferation in clear cell renal cell carcinoma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111577/ https://www.ncbi.nlm.nih.gov/pubmed/30066941 http://dx.doi.org/10.3892/or.2018.6590 |
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