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INTERNATIONAL CONGRESS OF

CancerGenetics

• Unraveling the Role of FGFR3 in Melanoma Progression: An Integrated Bioinformatics Approach to mRNA Expression and ceRNA Network Analysis.

• Mahdis Kashani,^1,* Zahra Rezvani,²
  1. Department of Cell and Molecular Biology, Univesity of Kashan, Kashan, Iran
  2. Department of Cell and Molecular Biology, Univesity of Kashan, Kashan, Iran
  
  
  
• Introduction: Melanoma, the most aggressive and deadliest form of skin cancer, originates from genetic mutations in melanocytes. These pigment-producing cells are found not only in the skin, but also in the eyes, inner ear, and leptomeninges. Beyond their coding counterparts, noncoding RNAs significantly impact gene expression at the post-transcriptional level, fostering elaborate RNA crosstalk in many pathological conditions, including cancer. A key mechanism involves competing endogenous RNAs (ceRNAs), which bind competitively to shared microRNAs (miRNAs). This study utilized microarrays to thoroughly analyze gene expression, aiming to identify new biomarkers for melanoma diagnosis and treatment.
• Methods: To identify potential biomarkers for melanoma, we first obtained the gene expression profile from the NCBI Gene Expression Omnibus (GEO) database, specifically dataset GSE46517. We then used GEO2R to perform a comparative analysis of gene expression between melanoma tissue and control samples. This analysis allowed us to pinpoint differentially expressed genes (DEGs), which were subsequently selected for further investigation in our study. We selected genes showing significant changes in expression (absolute log-fold change > 3 and p-value < 0.05) to find potential microRNAs (miRNAs) regulating them using miRWalk 3.0. Next, we searched LncBase v.3 to identify relevant long non-coding RNAs (lncRNAs) that could interact with these miRNAs, ultimately pinpointing RAB33B as a promising candidate. Finally, we used KEGG to analyze the biological gene pathways, helping us understand their specific role in cancer development.
• Results: Microarray analysis revealed FGFR3 as a significantly up-regulated mRNA, with a log-fold change of 4.46 and an adjusted p-value of 1.23E-12. Further analysis using miRWalk indicated a strong interaction between hsa-miR-409-3p and FGFR3 mRNA (score: 1, energy: -29.3). We then utilized the KEGG database to examine the pathways associated with FGFR3, identifying its involvement in EGFR tyrosine kinase inhibitor resistance, MAPK, RAS, Rap1, PI3K-Akt, and calcium signaling pathways, signaling pathways regulating the pluripotency of stem cells, and Regulation of the actin cytoskeleton. Additionally, our investigation noted that hsa-miR-409-3p strongly interacts with the RAB33B lncRNA.
• Conclusion: Based on our analysis, it appears that FGFR3, hsa-miR-409-3p, and RAB33B (acting as a competing endogenous RNA or ceRNA) form a crucial biological network that plays a significant role in melanoma. This suggests their potential importance in understanding and targeting the disease. The RAB family of proteins plays a significant role in various aspects of cancer, notably in the formation and secretion of extracellular vesicles (such as exosomes, microvesicles, and apoptotic bodies). Furthermore, RAB proteins are intricately linked to the maintenance and regulation of cancer stem cells (CSCs). FGFR3's involvement in a CeRNA network and its presence in key signaling pathways in melanoma suggest it could be a reliable biomarker for both diagnosis and prognosis of the cancer.
• Keywords: Melanoma, FGFR3, RAB33B, Biomarker