An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene

Fayeza Sadia Laskar; Md Nazmul Islam Bappy; Md Sowrov Hossain; Zenifer Alam; Dilruba Afrin; Sudeb Saha; Kazi Md Ali Zinnah

doi:10.1155/2023/9705159

An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene

Int J Genomics. 2023 May 9:2023:9705159. doi: 10.1155/2023/9705159. eCollection 2023.

Authors

Fayeza Sadia Laskar¹, Md Nazmul Islam Bappy^{1

2}, Md Sowrov Hossain^{1

3}, Zenifer Alam¹, Dilruba Afrin^{1

2}, Sudeb Saha^{4

5}, Kazi Md Ali Zinnah^{1

2}

Affiliations

¹ Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
² Department of Animal and Fish Biotechnology, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
³ Department of Pharmaceuticals and Industrial Biotechnology, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
⁴ Faculty of Veterinary, Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
⁵ Department of Dairy Science, Sylhet Agricultural University, Sylhet 3100, Bangladesh.

Abstract

Mesenchymal-epithelial transition (MET) factor is a proto-oncogene encoding tyrosine kinase receptor with hepatocyte growth factor (HGF) or scatter factor (SF). It is found on the human chromosome number 7 and regulates the diverse cellular mechanisms of the human body. The impact of mutations occurring in the MET gene is demonstrated by their detrimental effects on normal cellular functions. These mutations can change the structure and function of MET leading to different diseases such as lung cancer, neck cancer, colorectal cancer, and many other complex syndromes. Hence, the current study focused on finding deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) and their subsequent impact on the protein's structure and functions, which may contribute to the emergence of cancers. These nsSNPs were first identified utilizing computational tools like SIFT, PROVEAN, PANTHER-PSEP, PolyPhen-2, I-Mutant 2.0, and MUpro. A total of 45359 SNPs of MET gene were accumulated from the database of dbSNP, and among them, 1306 SNPs were identified as non-synonymous or missense variants. Out of all 1306 nsSNPs, 18 were found to be the most deleterious. Moreover, these nsSNPs exhibited substantial effects on structure, binding affinity with ligand, phylogenetic conservation, secondary structure, and post-translational modification sites of MET, which were evaluated using MutPred2, RaptorX, ConSurf, PSIPRED, and MusiteDeep, respectively. Also, these deleterious nsSNPs were accompanied by changes in properties of MET like residue charge, size, and hydrophobicity. These findings along with the docking results are indicating the potency of the identified SNPs to alter the structure and function of the protein, which may lead to the development of cancers. Nonetheless, Genome-wide association study (GWAS) studies and experimental research are required to confirm the analysis of these nsSNPs.