PMID- 36358305
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221126
IS  - 2079-7737 (Print)
IS  - 2079-7737 (Electronic)
IS  - 2079-7737 (Linking)
VI  - 11
IP  - 11
DP  - 2022 Nov 2
TI  - 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.
LID - 10.3390/biology11111604 [doi]
LID - 1604
AB  - 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.
FAU - Chai, Chuan-Yu
AU  - Chai CY
AD  - Department of Biological Science, Faculty of Science, Universiti Tunku Abdul 
      Rahman, Jalan Universiti, Bandar Barat, Kampar 31900, Malaysia.
FAU - Maran, Sathiya
AU  - Maran S
AUID- ORCID: 0000-0001-5617-901X
AD  - School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar 
      Sunway 47500, Malaysia.
FAU - Thew, Hin-Yee
AU  - Thew HY
AD  - School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar 
      Sunway 47500, Malaysia.
FAU - Tan, Yong-Chiang
AU  - Tan YC
AD  - School of Postgraduate Studies, International Medical University, Jalan Jalil 
      Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
FAU - Rahman, Nik Mohd Afizan Nik Abd
AU  - Rahman NMANA
AUID- ORCID: 0000-0003-4835-4687
AD  - Department of Cell and Molecular Biology, Faculty of Biotechnology and 
      Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, 
      Malaysia.
FAU - Cheng, Wan-Hee
AU  - Cheng WH
AD  - Faculty of Health and Life Sciences, INTI International University, Persiaran 
      Perdana BBN, Putra Nilai, Nilai 71800, Malaysia.
FAU - Lai, Kok-Song
AU  - Lai KS
AD  - Health Sciences Division, Abu Dhabi Women's College, Higher Colleges of 
      Technology, Abu Dhabi 41012, United Arab Emirates.
FAU - Loh, Jiun-Yan
AU  - Loh JY
AD  - Centre of Research for Advanced Aquaculture (CORAA), UCSI University, No. 1, 
      Jalan Menara Gading UCSI Height, Cheras, Kuala Lumpur 56000, Malaysia.
FAU - Yap, Wai-Sum
AU  - Yap WS
AD  - He & Ni Academy, Office Tower B, Northpoint Mid Valley City, Kuala Lumpur 59200, 
      Malaysia.
LA  - eng
PT  - Journal Article
DEP - 20221102
PL  - Switzerland
TA  - Biology (Basel)
JT  - Biology
JID - 101587988
PMC - PMC9688001
OTO - NOTNLM
OT  - HRAS
OT  - RAS/MAPK signaling pathway
OT  - diagnosis
OT  - nsSNPs
OT  - prognosis
COIS- The authors declare no conflict of interest.
EDAT- 2022/11/12 06:00
MHDA- 2022/11/12 06:01
PMCR- 2022/11/02
CRDT- 2022/11/11 01:04
PHST- 2022/08/12 00:00 [received]
PHST- 2022/09/28 00:00 [revised]
PHST- 2022/10/09 00:00 [accepted]
PHST- 2022/11/11 01:04 [entrez]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2022/11/12 06:01 [medline]
PHST- 2022/11/02 00:00 [pmc-release]
AID - biology11111604 [pii]
AID - biology-11-01604 [pii]
AID - 10.3390/biology11111604 [doi]
PST - epublish
SO  - Biology (Basel). 2022 Nov 2;11(11):1604. doi: 10.3390/biology11111604.