Staff View: Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer

Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer

The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alteratio...

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Main Authors:	Chai, Chuan-Yu, Maran, Sathiya, Thew, Hin-Yee, Tan, Yong-Chiang, Nik Abd Rahman, Nik Mohd Afizan, Cheng, Wan-Hee, Lai, Kok-Song, Loh, Jiun-Yan, Yap, Wai-Sum
Format:	Article
Published:	MDPI 2022
Online Access:	http://psasir.upm.edu.my/id/eprint/102829/ https://www.mdpi.com/2079-7737/11/11/1604
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spelling	my.upm.eprints.1028292024-06-23T00:22:04Z http://psasir.upm.edu.my/id/eprint/102829/ Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer Chai, Chuan-Yu Maran, Sathiya Thew, Hin-Yee Tan, Yong-Chiang Nik Abd Rahman, Nik Mohd Afizan Cheng, Wan-Hee Lai, Kok-Song Loh, Jiun-Yan Yap, Wai-Sum The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein–protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein–protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as “pathogenic” or “harmful”. Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein–protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan–Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer. MDPI 2022 Article PeerReviewed Chai, Chuan-Yu and Maran, Sathiya and Thew, Hin-Yee and Tan, Yong-Chiang and Nik Abd Rahman, Nik Mohd Afizan and Cheng, Wan-Hee and Lai, Kok-Song and Loh, Jiun-Yan and Yap, Wai-Sum (2022) Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer. Biology, 11 (11). art. no. 1604. pp. 1-16. ISSN 2079-7737 https://www.mdpi.com/2079-7737/11/11/1604 10.3390/biology11111604
institution	Universiti Putra Malaysia
building	UPM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Putra Malaysia
content_source	UPM Institutional Repository
url_provider	http://psasir.upm.edu.my/
description	The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein–protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein–protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as “pathogenic” or “harmful”. Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein–protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan–Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer.
format	Article
author	Chai, Chuan-Yu Maran, Sathiya Thew, Hin-Yee Tan, Yong-Chiang Nik Abd Rahman, Nik Mohd Afizan Cheng, Wan-Hee Lai, Kok-Song Loh, Jiun-Yan Yap, Wai-Sum
spellingShingle	Chai, Chuan-Yu Maran, Sathiya Thew, Hin-Yee Tan, Yong-Chiang Nik Abd Rahman, Nik Mohd Afizan Cheng, Wan-Hee Lai, Kok-Song Loh, Jiun-Yan Yap, Wai-Sum Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer
author_facet	Chai, Chuan-Yu Maran, Sathiya Thew, Hin-Yee Tan, Yong-Chiang Nik Abd Rahman, Nik Mohd Afizan Cheng, Wan-Hee Lai, Kok-Song Loh, Jiun-Yan Yap, Wai-Sum
author_sort	Chai, Chuan-Yu
title	Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer
title_short	Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer
title_full	Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer
title_fullStr	Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer
title_full_unstemmed	Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer
title_sort	predicting deleterious non-synonymous single nucleotide polymorphisms nssnps of hras gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer
publisher	MDPI
publishDate	2022
url	http://psasir.upm.edu.my/id/eprint/102829/ https://www.mdpi.com/2079-7737/11/11/1604
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score	13.211869

Predicting deleterious non-synonymous single nucleotide polymorphisms nsSNPs of HRAS gene and in-silico evaluation of their structural and functional consequences towards diagnosis and prognosis of cancer

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