The Effect of hsa-miR-۶۷۳۰-۵p on COL۱A۲ Gene Expression in Liver Cancer: Mutation Impact on Protein Function

Liver cancer, specifically hepatocellular carcinoma (HCC), is one of the most common and severe cancers, often linked to chronic liver diseases such as hepatitis and cirrhosis. Investigating the genetic factors involved in liver cancer is essential for improving diagnostic methods and treatment strategies. This study explores the Heparan Sulfate Proteoglycan (HSPG) pathway, which plays a critical role in the tumor microenvironment and regulates various signaling pathways that influence tumor growth, invasion, and metastasis. Through bioinformatics analysis, we examine how mutations in the COL۱A۲ gene impact the protein structure and how miRNA regulation, specifically hsa-miR-۶۷۳۰-۵p, affects its expression. Method: A relevant dataset (GSE۱۴۶۰۴۹) was downloaded from the Gene Expression Omnibus (GEO) and analyzed using GEO۲R. The gene with significantly increased expression was identified. The P-value and LogFC of the gene were validated using GEPIA۲. The target miRNA, hsa-miR-۶۷۳۰-۵p, was identified and found to have a meaningful correlation with the selected gene, analyzed via miRWalk. Additionally, the related signaling pathway was identified using ENRICHR and analyzed through KEGG. The mutation effect on the COL۱A۲ gene in the Collagen alpha-۲ (type I) chain protein was analyzed using the HOPE database, revealing differences in amino acids caused by the mutation. Results: The microarray data showed a significant increase in COL۱A۲ [removed]P-value: ۲.۵e-۰۷, Log FC: ۲.۵۶) in cancer samples compared to control samples. This was further confirmed by the GEPIA۲ database (P-value < ۰.۰۵). Moreover, hsa-miR-۶۷۳۰-۵p (binding=۱, seed=۱, energy=-۲۱.۷, position=۳’UTR) demonstrated a strong correlation with COL۱A۲ expression. According to the UNIPROT database, a mutation at the ۳۴۹th position of the COL۱A۲ protein, where glycine (G) is replaced by serine (S), was identified as potentially pathogenic. Conclusion: Proteoglycans (PGs) in the tumor microenvironment are key macromolecules influencing various cancer-related processes such as proliferation, adhesion, angiogenesis, and metastasis. These molecules, including cell-surface heparan sulfate proteoglycans like Syndecan, are crucial in healthy liver tissue. However, the overproduction of different types of proteoglycans can occur in diseased liver tissue. Overexpression of the COL۱A۲ gene may disrupt the HSPG pathway, potentially contributing to cancer development. The Collagen alpha-۲ (type I) chain protein is a structural protein, and mutations can alter its flexibility and function, leading to changes that may support cancer progression. The selected miRNA( hsa-miR-۶۷۳۰-۵p) appears to be a regulatory factor that may increase the risk of liver cancer by controlling COL۱A۲ gene expression.

کلیدواژه ها:

Liver cancer ، COL۱A۲ ، hsa-miR-۶۷۳۰-۵p ، Gene Mutation ، HSPG Pathway