Comparative Analysis of TRPM۱ and hsa-miR-۱۹۳a-۵p: Exploring Their Roles as Potential Biomarkers and Oncogenes in Melanoma

Introduction Metastatic melanoma is the most aggressive form of skin cancer and its incidence is rising globally. Given the high mortality rate associated with melanoma, identifying the pathways involved in its development, tumor progression and metastasis is essential for improving patient outcomes. TRPM۱ encodes a protein that belongs to the transient receptor potential melastatin subfamily of ion channels. Its promoter region contains four microphthalmia-binding sites and an M-box element, suggesting its expression in pigmented cells, such as those in the retina and skin. TRPM۱ acts as a nonspecific cation channel, allowing cations like Ca۲+ to cross the membrane. In this study, we used a systems biology approach to explore the interactions, expression patterns, and signaling pathways in melanoma patients. Materials and methods A comparison of gene expression between normal and melanoma samples using the GEO dataset GSE۲۳۸۲۰۷ identified distinct differences. The TRPM۱ was chosen for further investigation from the list of upregulated genes in SKCM after consulting the ENCORI and GEPIA ۲ databases (logFC: ۶.۷۸۲, adj. P. Val < ۰.۰۰۰۱). The GEPIA۲ database was additionally utilized to assess TRPM۱'s association with survival in SKCM. The Reactome database was used to determine the signaling pathways in which the TRPM۱ gene is active. Protein-protein interactions were analyzed using the STRING database. lncRNA interactions and miRNA interaction analyses were conducted using the lncRRIsearch and miRWalk online software, respectively. Results Microarray analysis indicates that TRPM۱ is a significant high exposed gene in melanoma samples. Patients with high levels of TRPM۱ have lower chance of survival compared to those with low levels. Pathway enrichment analysis indicates that TRPM۱ plays a role in MITF-M-dependent gene expression. MITF-M-dependent genes are essential for regulating cell cycle progression and proliferation rates in melanocytes. TRPM۱ has remarkable interaction with NYX, GRM۶, MTMR۱۰, and TYR proteins. TRPM۱ shows a significant interaction with has-miR-۱۹۳a-۵p (score: ۱, position: ۳' UTR, binding energy: -۲۵.۶). Additionally, LINC۰۰۹۸۷ influences the expression level of TRPM۱, with ۲۹ reported interactions. Conclusion miR-۱۹۳a-۵p regulates MITF-M-dependent gene expression by suppressing TRPM۱ mRNA levels through its interaction with the ۳' UTR. Database analyses highlight the significant role of TRPM۱ in melanoma, suggesting that it may act as a potential oncogene (with upregulated mRNA) and a diagnostic biomarker for the disease. Alterations in the expression levels of LINC۰۰۹۸۷ and miR-۱۹۳a-۵p, as well as disruptions in their interactions with TRPM۱, could elevate the risk of developing melanoma.

کلیدواژه ها:

Melanoma ، TRPM۱ ، MITF ، miR-۱۹۳a-۵p ، LINC۰۰۹۸۷