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Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma

BACKGROUND: Scavenger receptor class B type I (SR-BI) has been reported to be involved in carcinogenesis of several human cancers. However, it is currently unknown whether SR-BI plays a role in clear cell renal cell carcinoma (ccRCC). Here, we aimed to evaluate a tumor promotive mechanism for SR-BI...

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Autores principales: Xu, Guang-hua, Lou, Ning, Shi, Hang-chuan, Xu, Yu-chen, Ruan, Hai-long, Xiao, Wen, Liu, Lei, Li, Xiang, Xiao, Hai-bing, Qiu, Bin, Bao, Lin, Yuan, Chang-fei, Zhou, Ya-li, Hu, Wen-jun, Chen, Ke, Yang, Hong-mei, Zhang, Xiao-ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778766/
https://www.ncbi.nlm.nih.gov/pubmed/29357836
http://dx.doi.org/10.1186/s12885-017-3761-z
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author Xu, Guang-hua
Lou, Ning
Shi, Hang-chuan
Xu, Yu-chen
Ruan, Hai-long
Xiao, Wen
Liu, Lei
Li, Xiang
Xiao, Hai-bing
Qiu, Bin
Bao, Lin
Yuan, Chang-fei
Zhou, Ya-li
Hu, Wen-jun
Chen, Ke
Yang, Hong-mei
Zhang, Xiao-ping
author_facet Xu, Guang-hua
Lou, Ning
Shi, Hang-chuan
Xu, Yu-chen
Ruan, Hai-long
Xiao, Wen
Liu, Lei
Li, Xiang
Xiao, Hai-bing
Qiu, Bin
Bao, Lin
Yuan, Chang-fei
Zhou, Ya-li
Hu, Wen-jun
Chen, Ke
Yang, Hong-mei
Zhang, Xiao-ping
author_sort Xu, Guang-hua
collection PubMed
description BACKGROUND: Scavenger receptor class B type I (SR-BI) has been reported to be involved in carcinogenesis of several human cancers. However, it is currently unknown whether SR-BI plays a role in clear cell renal cell carcinoma (ccRCC). Here, we aimed to evaluate a tumor promotive mechanism for SR-BI in ccRCC. METHODS: The expression of SR-BI was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC) in ccRCC tissues and cell lines. Lipid droplets in ccRCC tissues and normal kidney tissues were examined by Oil Red O (ORO) and hematoxylin-eosin (HE) staining. The correlation between SR-BI mRNA levels and clinicopathological features was analyzed by Pearson’s chi-square test or Fisher’s exact test. Kaplan-Meier analysis and Cox model were used to evaluate the difference in progression-free survival (PFS) associated with expression of SR-BI. Inhibition of SR-BI was conducted by using small interfering RNA (siRNA). In vitro assays were performed to assess the impact of SR-BI knockdown on cell biological behaviors. High density lipoprotein (HDL)-cholesterol content in ccRCC cells and extracellular media was also measured after transfection with siRNA. RESULTS: The expression of SR-BI was markedly up-regulated in ccRCC tissues and tumor cell lines. ORO and HE staining revealed huge amounts of lipid droplets accumulation in ccRCC. Clinical analysis showed that over-expression of SR-BI was positively associated with tumor size, grade, distant metastasis and inversely correlated with PFS. Furthermore, SR-BI was proved to be an independent prognostic marker in ccRCC patients. The inhibition of SR-BI attenuated the tumorous behaviors of ccRCC cells, expression of metastasis and AKT pathway related proteins. The content of HDL-cholesterol was reduced in cells while increased in extracellular media after transfection with si-SR-BI. CONCLUSIONS: Our results demonstrate that SR-BI functions as an oncogene and promotes progression of ccRCC. SR-BI may serve as a potential prognostic biomarker and therapeutic target for ccRCC.
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spelling pubmed-57787662018-01-31 Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma Xu, Guang-hua Lou, Ning Shi, Hang-chuan Xu, Yu-chen Ruan, Hai-long Xiao, Wen Liu, Lei Li, Xiang Xiao, Hai-bing Qiu, Bin Bao, Lin Yuan, Chang-fei Zhou, Ya-li Hu, Wen-jun Chen, Ke Yang, Hong-mei Zhang, Xiao-ping BMC Cancer Research Article BACKGROUND: Scavenger receptor class B type I (SR-BI) has been reported to be involved in carcinogenesis of several human cancers. However, it is currently unknown whether SR-BI plays a role in clear cell renal cell carcinoma (ccRCC). Here, we aimed to evaluate a tumor promotive mechanism for SR-BI in ccRCC. METHODS: The expression of SR-BI was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC) in ccRCC tissues and cell lines. Lipid droplets in ccRCC tissues and normal kidney tissues were examined by Oil Red O (ORO) and hematoxylin-eosin (HE) staining. The correlation between SR-BI mRNA levels and clinicopathological features was analyzed by Pearson’s chi-square test or Fisher’s exact test. Kaplan-Meier analysis and Cox model were used to evaluate the difference in progression-free survival (PFS) associated with expression of SR-BI. Inhibition of SR-BI was conducted by using small interfering RNA (siRNA). In vitro assays were performed to assess the impact of SR-BI knockdown on cell biological behaviors. High density lipoprotein (HDL)-cholesterol content in ccRCC cells and extracellular media was also measured after transfection with siRNA. RESULTS: The expression of SR-BI was markedly up-regulated in ccRCC tissues and tumor cell lines. ORO and HE staining revealed huge amounts of lipid droplets accumulation in ccRCC. Clinical analysis showed that over-expression of SR-BI was positively associated with tumor size, grade, distant metastasis and inversely correlated with PFS. Furthermore, SR-BI was proved to be an independent prognostic marker in ccRCC patients. The inhibition of SR-BI attenuated the tumorous behaviors of ccRCC cells, expression of metastasis and AKT pathway related proteins. The content of HDL-cholesterol was reduced in cells while increased in extracellular media after transfection with si-SR-BI. CONCLUSIONS: Our results demonstrate that SR-BI functions as an oncogene and promotes progression of ccRCC. SR-BI may serve as a potential prognostic biomarker and therapeutic target for ccRCC. BioMed Central 2018-01-22 /pmc/articles/PMC5778766/ /pubmed/29357836 http://dx.doi.org/10.1186/s12885-017-3761-z Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Xu, Guang-hua
Lou, Ning
Shi, Hang-chuan
Xu, Yu-chen
Ruan, Hai-long
Xiao, Wen
Liu, Lei
Li, Xiang
Xiao, Hai-bing
Qiu, Bin
Bao, Lin
Yuan, Chang-fei
Zhou, Ya-li
Hu, Wen-jun
Chen, Ke
Yang, Hong-mei
Zhang, Xiao-ping
Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma
title Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma
title_full Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma
title_fullStr Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma
title_full_unstemmed Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma
title_short Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma
title_sort up-regulation of sr-bi promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778766/
https://www.ncbi.nlm.nih.gov/pubmed/29357836
http://dx.doi.org/10.1186/s12885-017-3761-z
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