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In vitro and In silico Analysis of SCIN rs376349889 as a Potential Biomarker for Gastric and Colorectal Cancers
Neda Vaghefinezhad1, Mansoureh Azadeh2, Majid Tafrihi1
1Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran.
Background:
Numerous research endeavors have reported altered expression of Scinderin (SCIN) in various cancer types. Single Nucleotide Polymorphisms (SNPs) represent the most prevalent form of genetic variation within the human genome which can have significant functional consequences, including cancer predisposition.
Methods:
This study investigated SNP-induced structural alterations in the SCIN protein and their potential effects on stability and function, using in vitro and in silico approaches. Integrating experimental and computational data provides insight into the role of this variant in tumorigenesis and highlights its potential as a molecular biomarker for cancer diagnosis and prognosis.
Results:
Out of 1,054 nonsynonymous SNPs (nsSNPs), 11 were consistently predicted to be deleterious. Among them, rs376349889 (R511G) was associated with decreased protein stability, loss of ADP-ribosylation at R511, disrupted ionic interactions, and increased hydrophobicity, all of which may impair SCIN function. Subsequently, genotyping of 200 colorectal cancer and 200 gastric cancer samples for the rs376349889 SNP was performed using High-Resolution Melting (HRM) technique in compared to a matched control group.
Conclusion:
The findings revealed a considerable difference in the allelic prevalence of the rs376349889 SNP between cancer patients and control samples. Notably, the GG genotype was linked to a higher susceptibility to both gastric and colorectal cancers (p<0.0001). These results suggest that rs376349889 may influence SCIN-related oncogenic mechanisms and could serve as a promising biomarker for identifying or evaluating the risk of gastrointestinal cancers at an early stage.
