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, 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). 1604.

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Abstract

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.

Item ID:	83352
Item Type:	Article (Research - C1)
ISSN:	2079-7737
Copyright Information:	© 2022 by the authors. 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/).
Date Deposited:	06 Aug 2024 21:57
FoR Codes:	31 BIOLOGICAL SCIENCES > 3105 Genetics > 310509 Genomics @ 100%
SEO Codes:	20 HEALTH > 2099 Other health > 209999 Other health not elsewhere classified @ 100%
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