The influence of ERBB۴ gene expression and its genetic modification on kidney renal cell carcinoma

Introduction Kidney renal cell carcinoma (KIRC) is the most common subtype of kidney cancer, accounting for ۷۵% of cases and associated with high mortality. Genetic factors play a crucial role in KIRC's pathogenesis, and understanding these genetic elements may lead to targeted therapies and improved patient outcomes. Methods We obtained the dataset GSE۱۶۸۸۴۵ from the Gene Expression Omnibus (GEO) and analyzed it using GEO۲R. A gene showing significant decreased expression was identified through ENCORI and GEPIA۲ databases. A specific miRNA was selected based on its strong correlation with this gene, analyzed via miRWalk. The associated signaling pathways were assessed using the KEGG database. We investigated single nucleotide polymorphisms (SNPs) linked to the gene using the SIFT, miRNASNP, and dbSNP databases. We focused on an SNP in the ۳' untranslated region (UTR) and another within the coding sequence, evaluating their potential impacts through the HOPE database. Protein interactions related to the gene were explored using the STRING database. Results The ERBB۴ gene was selected, showing a log fold change (logFC) of -۷.۵۸۳۷۶۰۷ and an adjusted p-value (adj.P.Val) of ۰.۰۰۳۰۵۹۰۱. The SNP rs۱۴۱۸۸۲۱۶۹۴, affecting the ۳' UTR, was identified via miRNASNP. Another SNP, rs۲۶۷۵۹۹۱۹۲, located in the coding sequence, was found to change the amino acid at position ۵۴۴ from Arginine to Tryptophan. This mutation, according to the HOPE database, suggests that the larger mutant residue may cause structural abnormalities. The wild-type residue has a positive charge, while the mutant is neutral and more hydrophobic, likely disrupting hydrogen bonding and protein folding. These changes may adversely impact protein functionality. The KEGG database indicated that the ERBB signaling pathway may be crucial in KIRC development. The miRNA hsa-miR-۷۱۵۲-۳p was identified as influencing the ۳' UTR with high binding probability of ۱, a seed region of ۱ and energy value of -۲۷. The long non-coding RNA HELLPAR was associated with the ERBB۴ gene according to LncRRIsearch. Conclusion The ERBB۴ gene, linked to the ERBB signaling pathway, likely contributes to KIRC development through reduced expression, as observed in affected patients. The SNPs rs۱۴۱۸۸۲۱۶۹۴ and rs۲۶۷۵۹۹۱۹۲ may further decrease gene expression. Additionally, the microRNA hsa-miR-۷۱۵۲-۳p and long non-coding RNA HELLPAR are implicated in the downregulation of ERBB۴, suggesting their roles in KIRC pathogenesis.

کلیدواژه ها:

ERBB۴ ، KIRC ، hsa-miR-۷۱۵۲-۳p ، HELLPAR ، ERBB signaling pathway