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Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4
BACKGROUND: Endothelial DLL4 plays an important role in controlling of tumor angiogenesis, which is required for tumor invasive growth and metastasis. However, the regulation of DLL4 in clear cell renal cell carcinoma (ccRCC) has not yet been systematically elucidated. METHODOLOGY: We performed bioi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694928/ https://www.ncbi.nlm.nih.gov/pubmed/23826258 http://dx.doi.org/10.1371/journal.pone.0067294 |
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author | Huang, Qing Bo Ma, Xin Zhang, Xu Liu, Shang Wen Ai, Qing Shi, Tao Ping Zhang, Yu Gao, Yu Fan, Yang Ni, Dong Wang, Bao Jun Li, Hong Zhao Zheng, Tao |
author_facet | Huang, Qing Bo Ma, Xin Zhang, Xu Liu, Shang Wen Ai, Qing Shi, Tao Ping Zhang, Yu Gao, Yu Fan, Yang Ni, Dong Wang, Bao Jun Li, Hong Zhao Zheng, Tao |
author_sort | Huang, Qing Bo |
collection | PubMed |
description | BACKGROUND: Endothelial DLL4 plays an important role in controlling of tumor angiogenesis, which is required for tumor invasive growth and metastasis. However, the regulation of DLL4 in clear cell renal cell carcinoma (ccRCC) has not yet been systematically elucidated. METHODOLOGY: We performed bioinformatical analysis to explore miRNAs targeting DLL4. miR-30a was selected as a representative to validate its functional association in endothelial cell. Then, the expressions of DLL4 and mature miR-30a from 90 cases of ccRCC and 28 cases of nonmatched adjacent non-tumor tissues were measured by quantitative real-time PCR. Finally, the expression of miR-30a was correlated with DLL4 expression, tumor features (metastatic condition and microvessel density), and patient metastasis-free survival. The univariate and multivariate analyses were performed to select the risk factors associated with hematogenous metastasis, respectively. PRINCIPAL FINDINGS: miR-30a negatively regulated DLL4 and inhibited the proliferation and migration of endothelial cells. DLL4 was up-regulated in ccRCC and further increased in hematogenous metastatic cases, while miR-30a was down-regulated in tumor tissues and further decreased in hematogenous metastatic ccRCC (student t test, all p<0.05). Additionally, expression of miR-30a was inversely correlated with expression of DLL4 and microvessel density (linear correlation analysis, both p<0.05). Low-level miR-30a also indicated a higher probability of developing metastasis (log-rank test, p = 0.010). Most importantly, miR-30a expression was an independent predictor of ccRCC hematogenous metastasis by the univariate analysis and binary logistic regression model (both p<0.05). CONCLUSIONS: Down-regulated miR-30a in ccRCC was associated with tumor hematogenous metastasis through increasing microvessel density by targeting angiogenesis-specific DLL4. |
format | Online Article Text |
id | pubmed-3694928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36949282013-07-03 Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4 Huang, Qing Bo Ma, Xin Zhang, Xu Liu, Shang Wen Ai, Qing Shi, Tao Ping Zhang, Yu Gao, Yu Fan, Yang Ni, Dong Wang, Bao Jun Li, Hong Zhao Zheng, Tao PLoS One Research Article BACKGROUND: Endothelial DLL4 plays an important role in controlling of tumor angiogenesis, which is required for tumor invasive growth and metastasis. However, the regulation of DLL4 in clear cell renal cell carcinoma (ccRCC) has not yet been systematically elucidated. METHODOLOGY: We performed bioinformatical analysis to explore miRNAs targeting DLL4. miR-30a was selected as a representative to validate its functional association in endothelial cell. Then, the expressions of DLL4 and mature miR-30a from 90 cases of ccRCC and 28 cases of nonmatched adjacent non-tumor tissues were measured by quantitative real-time PCR. Finally, the expression of miR-30a was correlated with DLL4 expression, tumor features (metastatic condition and microvessel density), and patient metastasis-free survival. The univariate and multivariate analyses were performed to select the risk factors associated with hematogenous metastasis, respectively. PRINCIPAL FINDINGS: miR-30a negatively regulated DLL4 and inhibited the proliferation and migration of endothelial cells. DLL4 was up-regulated in ccRCC and further increased in hematogenous metastatic cases, while miR-30a was down-regulated in tumor tissues and further decreased in hematogenous metastatic ccRCC (student t test, all p<0.05). Additionally, expression of miR-30a was inversely correlated with expression of DLL4 and microvessel density (linear correlation analysis, both p<0.05). Low-level miR-30a also indicated a higher probability of developing metastasis (log-rank test, p = 0.010). Most importantly, miR-30a expression was an independent predictor of ccRCC hematogenous metastasis by the univariate analysis and binary logistic regression model (both p<0.05). CONCLUSIONS: Down-regulated miR-30a in ccRCC was associated with tumor hematogenous metastasis through increasing microvessel density by targeting angiogenesis-specific DLL4. Public Library of Science 2013-06-27 /pmc/articles/PMC3694928/ /pubmed/23826258 http://dx.doi.org/10.1371/journal.pone.0067294 Text en © 2013 Huang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Huang, Qing Bo Ma, Xin Zhang, Xu Liu, Shang Wen Ai, Qing Shi, Tao Ping Zhang, Yu Gao, Yu Fan, Yang Ni, Dong Wang, Bao Jun Li, Hong Zhao Zheng, Tao Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4 |
title | Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4 |
title_full | Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4 |
title_fullStr | Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4 |
title_full_unstemmed | Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4 |
title_short | Down-Regulated miR-30a in Clear Cell Renal Cell Carcinoma Correlated with Tumor Hematogenous Metastasis by Targeting Angiogenesis-Specific DLL4 |
title_sort | down-regulated mir-30a in clear cell renal cell carcinoma correlated with tumor hematogenous metastasis by targeting angiogenesis-specific dll4 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694928/ https://www.ncbi.nlm.nih.gov/pubmed/23826258 http://dx.doi.org/10.1371/journal.pone.0067294 |
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