Rs۳۵۱۰۷۹۶۲ modifies Microtubule Cytoskeleton Organization via Frameshift in MAP۷ Gene and Protein in Skin Cancer patients: in-silico investigation

The skin cancer known as cutaneous melanoma (SKCM) arises from melanocytes, which arecells that produce pigment. This type of cancer is particularly aggressive and often fatal [۱]. Epithelialmesenchymaltransition (EMT) is a process commonly observed in malignant skin tumors [۴]. MAP۷,also called Ensconsin, is a protein that stabilizes microtubules and may play a crucial role in organizingthe cytoskeleton and microtubules. This study sought to explore a new regulatory biomarker in skincancer patients using an integrated approach involving bioinformatics and systems biology analysis.Microarray profiling analysis and gene expression data assessment were conducted using the GSE۷۳۶۵۲database with GEO۲R. GEPIA۲ was used to examine the correlation between the gene and skincutaneous melanoma. Single Nucleotide Polymorphisms (SNPs) of the gene were extracted frommiRNASNP and biological pathway analysis was performed using Enrichr. The protein structurechanges caused by the single nucleotide variations were studied using the Hope database and theAlphafold artificial intelligence program [۳]. sorting intolerant from tolerant SNPs was predicted usingthe SIFT database .The microarray analysis revealed a significant downregulation of the MAP۷ gene in skin cutaneousmelanoma patients. Further investigation indicated that the product of the MAP۷ gene is a microtubuleassociatedprotein predominantly expressed in epithelial cells. The process of cell invasion andmigration relies on the dynamic changes taking place in the cytoskeletal components such as actin andtubulin [۲]. Changes in cellular architecture by internal clues will affect the cell functions leading to theformation of different protrusions that helps cell migration eventually leading to metastasis [۲]. Ouranalysis also revealed that a single nucleotide variant(C>G) in the protein-coding sequence(CDS)region caused the mutation of an Arginine into a Proline at position ۵۱۲. This mutation can disruptan α-helix which affects the structure and function of the protein [۳].

کلیدواژه ها:

EMT ، MAP۷ ، Skin Cancer ، Microtubule Organization