Abstract:
Breast cancer remains a significant global health concern, constituting
around 12% of all cancer incidences worldwide, affecting millions of
women and posing substantial challenges to both patients and healthcare
providers. KLF7 is zinc-finger like protein, has emerged as a promising
candidate in the context of cancer research due to its significance in
regulating gene expression and cellular processes. In this study, Alpha Fold was used for the 3-D structure prediction of KLF7. DynaMut,
MUpro, and Maestro were utilized for estimating the impact SNPs on the
stability of protein. Hope and MutPred2 highlighted significant
structural and functional impacts of the mutations. Molecular dynamics
(MD) Simulations were employed to elucidate the conformational
behavior and dynamics properties of protein KLF7. Finally, genotype
analysis was performed to investigate the association between breast
cancer and KLF7. This study identifies, for the first time, a single
nucleotide polymorphism (SNP), rs941470359 of KLF7gene that
significantly decreases protein stability and contributes to the induction
of breast cancer. The results of MD simulations, which include RMSD,
RMSF, and Rg, confirmed significant differences between the mutant and
XXIII
wild-type proteins. Furthermore, genotype analysis, supported by OR
and RR values of 2.584 and 1.587, respectively, demonstrated a
substantial correlation between the homozygous wild-type genotype (CC)
and incidence of breast cancer. These results highlight the pathogenic
potential of rs941470359 in breast cancer progression and suggests that
further investigation into the role of KLF7 in breast cancer could lead to
significant advancements in understanding cancer research, timely
diagnosis and developing targeted therapeutic strategies.
