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FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway

OBJECTIVE: Herein, we aimed at exploring the FAP expression in clear cell renal cell carcinoma (ccRCC) along with its clinical implication. METHODS: Using computational tools analysis of different freely accessible gene databases, the expression pattern, clinical importance, co-expressed genes, and...

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Autores principales: Jiang, Kun, Xu, Li-zhe, Ning, Jin-zhuo, Cheng, Fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523722/
https://www.ncbi.nlm.nih.gov/pubmed/37752545
http://dx.doi.org/10.1186/s12935-023-03073-8
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author Jiang, Kun
Xu, Li-zhe
Ning, Jin-zhuo
Cheng, Fan
author_facet Jiang, Kun
Xu, Li-zhe
Ning, Jin-zhuo
Cheng, Fan
author_sort Jiang, Kun
collection PubMed
description OBJECTIVE: Herein, we aimed at exploring the FAP expression in clear cell renal cell carcinoma (ccRCC) along with its clinical implication. METHODS: Using computational tools analysis of different freely accessible gene databases, the expression pattern, clinical importance, co-expressed genes, and signaling pathways of FAP in ccRCC were thoroughly investigated. FAP expression was examined in clinical ccRCC specimens through qRT-PCR, western blotting and immunohistochemistry. Furthermore, in vitro and in vivo experiments were carried out using flow cytometry, CCK-8, wound-healing and Transwell assays, as well as xenograft tumor model, respectively. RESULTS: FAP levels were found to be significantly elevated in ccRCC based on bioinformatic data from public databases. Patients who exhibited higher expression levels of FAP had poorer prognoses, according to Kaplan–Meier analysis of survival data. In addition, diagnostic and prognostic value of FAP in ccRCC was figured out by ROC curve and prognostic nomogram model. In vitro study revealed that the over-expression FAP accelerated cell proliferation, migration as well as invasion, and suppressed cell apoptosis, but silencing of FAP had the opposite effect. FAP suppression reduced the PI3K/AKT/mTOR pathway's stimulation, whereas FAP up-regulation increased the stimulation of the pathway. Blocking the PI3K/AKT/mTOR signaling pathway with the dual PI3K/mTOR inhibitor BEZ235 repressesed cancer-promoting effect of FAP. Additionally, we found that the downregulation of FAP was effective at slowing tumor progression in vivo. CONCLUSION: It is possible that FAP could be a reliable biomarker for the diagnosis and prognosis of ccRCC because of its role in the ccRCC progression via triggering the PI3K/AKT/mTOR signaling pathway.
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spelling pubmed-105237222023-09-28 FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway Jiang, Kun Xu, Li-zhe Ning, Jin-zhuo Cheng, Fan Cancer Cell Int Research OBJECTIVE: Herein, we aimed at exploring the FAP expression in clear cell renal cell carcinoma (ccRCC) along with its clinical implication. METHODS: Using computational tools analysis of different freely accessible gene databases, the expression pattern, clinical importance, co-expressed genes, and signaling pathways of FAP in ccRCC were thoroughly investigated. FAP expression was examined in clinical ccRCC specimens through qRT-PCR, western blotting and immunohistochemistry. Furthermore, in vitro and in vivo experiments were carried out using flow cytometry, CCK-8, wound-healing and Transwell assays, as well as xenograft tumor model, respectively. RESULTS: FAP levels were found to be significantly elevated in ccRCC based on bioinformatic data from public databases. Patients who exhibited higher expression levels of FAP had poorer prognoses, according to Kaplan–Meier analysis of survival data. In addition, diagnostic and prognostic value of FAP in ccRCC was figured out by ROC curve and prognostic nomogram model. In vitro study revealed that the over-expression FAP accelerated cell proliferation, migration as well as invasion, and suppressed cell apoptosis, but silencing of FAP had the opposite effect. FAP suppression reduced the PI3K/AKT/mTOR pathway's stimulation, whereas FAP up-regulation increased the stimulation of the pathway. Blocking the PI3K/AKT/mTOR signaling pathway with the dual PI3K/mTOR inhibitor BEZ235 repressesed cancer-promoting effect of FAP. Additionally, we found that the downregulation of FAP was effective at slowing tumor progression in vivo. CONCLUSION: It is possible that FAP could be a reliable biomarker for the diagnosis and prognosis of ccRCC because of its role in the ccRCC progression via triggering the PI3K/AKT/mTOR signaling pathway. BioMed Central 2023-09-27 /pmc/articles/PMC10523722/ /pubmed/37752545 http://dx.doi.org/10.1186/s12935-023-03073-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jiang, Kun
Xu, Li-zhe
Ning, Jin-zhuo
Cheng, Fan
FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway
title FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway
title_full FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway
title_fullStr FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway
title_full_unstemmed FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway
title_short FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway
title_sort fap promotes clear cell renal cell carcinoma progression via activating the pi3k/akt/mtor signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523722/
https://www.ncbi.nlm.nih.gov/pubmed/37752545
http://dx.doi.org/10.1186/s12935-023-03073-8
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