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In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis

Dysregulation of fibroblast growth factors is linked to the pathogenesis of bladder cancer. The role of FGF1 and FGF3 is evident in bladder cancer; however, the role of FGF4 is vague. Despite being reported that FGF4 interacts with FGF1 and FGF3 in MAPK pathways, its pathogenesis and mechanism of ac...

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Autores principales: Lim, Ee Chen, Lim, Shu Wen, Tan, Kenneth JunKai, Sathiya, Maran, Cheng, Wan Hee, Lai, Kok-Song, Loh, Jiun-Yan, Yap, Wai-Sum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316931/
https://www.ncbi.nlm.nih.gov/pubmed/35888106
http://dx.doi.org/10.3390/life12071018
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author Lim, Ee Chen
Lim, Shu Wen
Tan, Kenneth JunKai
Sathiya, Maran
Cheng, Wan Hee
Lai, Kok-Song
Loh, Jiun-Yan
Yap, Wai-Sum
author_facet Lim, Ee Chen
Lim, Shu Wen
Tan, Kenneth JunKai
Sathiya, Maran
Cheng, Wan Hee
Lai, Kok-Song
Loh, Jiun-Yan
Yap, Wai-Sum
author_sort Lim, Ee Chen
collection PubMed
description Dysregulation of fibroblast growth factors is linked to the pathogenesis of bladder cancer. The role of FGF1 and FGF3 is evident in bladder cancer; however, the role of FGF4 is vague. Despite being reported that FGF4 interacts with FGF1 and FGF3 in MAPK pathways, its pathogenesis and mechanism of action are yet to be elucidated. Therefore, this study aimed to elucidate pathogenic nsSNPs and their role in the prognosis of bladder cancer by employing in-silico analysis. The nsSNPs of FGF4 were retrieved from the NCBI database. Different in silico tools, PROVEAN, SIFT, PolyPhen-2, SNPs&GO, and PhD-SNP, were used for predicting the pathogenicity of the nsSNPs. Twenty-seven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MUPro indicated 22 nsSNPs to cause decreased stability (DDG scores < −0.5). Conservation analysis predicted that Q97K, G106V, N164S, and N167S were highly conserved and exposed. Biophysical characterisation indicated these nsSNPs were not tolerated, and protein-protein interaction analysis showed their involvement in the GFR-MAPK signalling pathway. Furthermore, Kaplan Meier bioinformatics analyses indicated that the FGF4 gene deregulation affected the overall survival rate of patients with bladder cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of FGF4 may serve as potential targets for diagnoses and therapeutic interventions focusing on bladder cancer.
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spelling pubmed-93169312022-07-27 In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis Lim, Ee Chen Lim, Shu Wen Tan, Kenneth JunKai Sathiya, Maran Cheng, Wan Hee Lai, Kok-Song Loh, Jiun-Yan Yap, Wai-Sum Life (Basel) Article Dysregulation of fibroblast growth factors is linked to the pathogenesis of bladder cancer. The role of FGF1 and FGF3 is evident in bladder cancer; however, the role of FGF4 is vague. Despite being reported that FGF4 interacts with FGF1 and FGF3 in MAPK pathways, its pathogenesis and mechanism of action are yet to be elucidated. Therefore, this study aimed to elucidate pathogenic nsSNPs and their role in the prognosis of bladder cancer by employing in-silico analysis. The nsSNPs of FGF4 were retrieved from the NCBI database. Different in silico tools, PROVEAN, SIFT, PolyPhen-2, SNPs&GO, and PhD-SNP, were used for predicting the pathogenicity of the nsSNPs. Twenty-seven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MUPro indicated 22 nsSNPs to cause decreased stability (DDG scores < −0.5). Conservation analysis predicted that Q97K, G106V, N164S, and N167S were highly conserved and exposed. Biophysical characterisation indicated these nsSNPs were not tolerated, and protein-protein interaction analysis showed their involvement in the GFR-MAPK signalling pathway. Furthermore, Kaplan Meier bioinformatics analyses indicated that the FGF4 gene deregulation affected the overall survival rate of patients with bladder cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of FGF4 may serve as potential targets for diagnoses and therapeutic interventions focusing on bladder cancer. MDPI 2022-07-09 /pmc/articles/PMC9316931/ /pubmed/35888106 http://dx.doi.org/10.3390/life12071018 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lim, Ee Chen
Lim, Shu Wen
Tan, Kenneth JunKai
Sathiya, Maran
Cheng, Wan Hee
Lai, Kok-Song
Loh, Jiun-Yan
Yap, Wai-Sum
In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis
title In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis
title_full In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis
title_fullStr In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis
title_full_unstemmed In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis
title_short In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis
title_sort in-silico analysis of deleterious snps of fgf4 gene and their impacts on protein structure, function and bladder cancer prognosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316931/
https://www.ncbi.nlm.nih.gov/pubmed/35888106
http://dx.doi.org/10.3390/life12071018
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