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FBXL6 depletion restrains clear cell renal cell carcinoma progression

BACKGROUND: F-box proteins play important roles in cell cycle and tumorigenesis. However, its prognostic value and molecular function in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, we established a survival model to evaluate the prognosis of patients with ccRCC using the F...

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Autores principales: Yu, Yongchun, Yao, Wenhao, Wang, Tengda, Xue, Wei, Meng, Yuyang, Cai, Licheng, Jian, Wengang, Yu, Yipeng, Zhang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526225/
https://www.ncbi.nlm.nih.gov/pubmed/36183674
http://dx.doi.org/10.1016/j.tranon.2022.101550
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author Yu, Yongchun
Yao, Wenhao
Wang, Tengda
Xue, Wei
Meng, Yuyang
Cai, Licheng
Jian, Wengang
Yu, Yipeng
Zhang, Cheng
author_facet Yu, Yongchun
Yao, Wenhao
Wang, Tengda
Xue, Wei
Meng, Yuyang
Cai, Licheng
Jian, Wengang
Yu, Yipeng
Zhang, Cheng
author_sort Yu, Yongchun
collection PubMed
description BACKGROUND: F-box proteins play important roles in cell cycle and tumorigenesis. However, its prognostic value and molecular function in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, we established a survival model to evaluate the prognosis of patients with ccRCC using the F-box gene signature and investigated the function of FBXL6 in ccRCC. METHODS: Comprehensive bioinformatics analyses were used to identify differentially expressed F-box and hub genes associated with ccRCC carcinogenesis. Based on the F-box gene signature, we constructed a risk model and nomogram to predict the overall survival (OS) of patients with ccRCC and assist clinicians in decision-making. Finally, we verified the function and underlying molecular mechanisms of FBXL6 in ccRCC using CCK-8 and EdU assays, flow cytometry, and subcutaneous xenografts. RESULTS: A risk model based on FBXO39, FBXL6, FBXO1, and FBXL16 was developed. In addition, we drew a nomogram based on the risk score and clinical features to assess the prognosis of patients with ccRCC. Subsequently, we identified FBXL6 as an independent prognostic marker that was highly expressed in ccRCC cell lines. In vivo and in vitro assays revealed that the depletion of FBXL6 inhibited cell proliferation and induced apoptosis. We also demonstrated that SP1 regulated the expression of FBXL6. CONCLUSIONS: FBXL6 was first identified as a diagnostic and prognostic marker in patients with ccRCC. Loss of FBXL6 attenuates proliferation and induces apoptosis in ccRCC cells. SP1 was also found to regulate the expression of FBXL6.
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spelling pubmed-95262252022-10-07 FBXL6 depletion restrains clear cell renal cell carcinoma progression Yu, Yongchun Yao, Wenhao Wang, Tengda Xue, Wei Meng, Yuyang Cai, Licheng Jian, Wengang Yu, Yipeng Zhang, Cheng Transl Oncol Original Research BACKGROUND: F-box proteins play important roles in cell cycle and tumorigenesis. However, its prognostic value and molecular function in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, we established a survival model to evaluate the prognosis of patients with ccRCC using the F-box gene signature and investigated the function of FBXL6 in ccRCC. METHODS: Comprehensive bioinformatics analyses were used to identify differentially expressed F-box and hub genes associated with ccRCC carcinogenesis. Based on the F-box gene signature, we constructed a risk model and nomogram to predict the overall survival (OS) of patients with ccRCC and assist clinicians in decision-making. Finally, we verified the function and underlying molecular mechanisms of FBXL6 in ccRCC using CCK-8 and EdU assays, flow cytometry, and subcutaneous xenografts. RESULTS: A risk model based on FBXO39, FBXL6, FBXO1, and FBXL16 was developed. In addition, we drew a nomogram based on the risk score and clinical features to assess the prognosis of patients with ccRCC. Subsequently, we identified FBXL6 as an independent prognostic marker that was highly expressed in ccRCC cell lines. In vivo and in vitro assays revealed that the depletion of FBXL6 inhibited cell proliferation and induced apoptosis. We also demonstrated that SP1 regulated the expression of FBXL6. CONCLUSIONS: FBXL6 was first identified as a diagnostic and prognostic marker in patients with ccRCC. Loss of FBXL6 attenuates proliferation and induces apoptosis in ccRCC cells. SP1 was also found to regulate the expression of FBXL6. Neoplasia Press 2022-09-29 /pmc/articles/PMC9526225/ /pubmed/36183674 http://dx.doi.org/10.1016/j.tranon.2022.101550 Text en © 2022 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Yu, Yongchun
Yao, Wenhao
Wang, Tengda
Xue, Wei
Meng, Yuyang
Cai, Licheng
Jian, Wengang
Yu, Yipeng
Zhang, Cheng
FBXL6 depletion restrains clear cell renal cell carcinoma progression
title FBXL6 depletion restrains clear cell renal cell carcinoma progression
title_full FBXL6 depletion restrains clear cell renal cell carcinoma progression
title_fullStr FBXL6 depletion restrains clear cell renal cell carcinoma progression
title_full_unstemmed FBXL6 depletion restrains clear cell renal cell carcinoma progression
title_short FBXL6 depletion restrains clear cell renal cell carcinoma progression
title_sort fbxl6 depletion restrains clear cell renal cell carcinoma progression
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526225/
https://www.ncbi.nlm.nih.gov/pubmed/36183674
http://dx.doi.org/10.1016/j.tranon.2022.101550
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