MIR497HG/hsa-miR-4766-3p/KRT31 CeRNA axis affects Skin Cutaneous Melanoma development by regulating Keratinization signaling pathway & Estrogen signaling pathway: integrated gene expression profiling and systems biology analyses
MIR497HG/hsa-miR-4766-3p/KRT31 CeRNA axis affects Skin Cutaneous Melanoma development by regulating Keratinization signaling pathway & Estrogen signaling pathway: integrated gene expression profiling and systems biology analyses
Ali Ghaneh,1Mohammad Rezaei,2Mansoureh Azadeh,3,*
1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran 2. Department of Biology and Biotechnology, University of Pavia, Pavia, Italy 3. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
Introduction: Skin cutaneous melanoma (SKCM) is a highly lethal type of skin cancer with a significant global mortality rate. The identification of reliable prognostic biomarkers and potential therapeutic targets is crucial for improving melanoma treatment outcomes. Recent studies have demonstrated the critical involvement of long non-coding RNA (lncRNA) in the regulation of gene expression in various diseases and tumors. Consequently, investigating the role of lncRNAs in the progression and advancement of SKCM is of utmost importance (1).
Defining a competitive endogenous RNA(CeRNA) network provides valuable biomarkers and boosts the treatment process. CeRna theory claims that RNAs compete for a limited number of miRNAs; this competition affects the regulation of the cell. In cancer, the relationship between the components of this network changes (compared to the normal condition) and provides valuable information about the disease and its stage.
Methods: To begin with, GSE160902 has been chosen from NCBI Gene Expression Omnibus (GEO) and was analyzed with GEO2R in order to find gene with significant Decrease in expression regulation. KRT31 gene was chosen and its downregulation in (SKCM) was validated by the ENCORI database(2)(3). Using KEGG pathway database and Reactom gene ontology and biology pathways were determined (4)(5). miRNA interacting with KRT31 was obtained from miRWalk database(6).
LncRNAs that have interaction with miRNA were acquired from LncBase v.3 the interaction between miRNA/LncRNA and miRNA/KRT31 were validated by ENCORI co_Expression analysis. Finaliy Cytoscape 3.9.1 was used to visualize ceRNA network.
Results: Based on GSE160902, 104 up and down regulated gene were determined. KRT31 down regulated gene were selected among these ups and down which has a interaction in Keratinization signaling and Estrogen signaling pathway. Compared to control (LogFC: -2.6192) (adj.P.Val < 0.001). GEPIA2 and ENCORI expression analysis validates the expression analysis results. Based on survival analysis the low expression of KRT31 has a significant positive correlation with the survival rate of SKCM cancer( HR:1.62 logrank p: 0.00079). hsa-miR-4766-3p miRNAs was extracted from miRWalk 3.0. In addition, MIR497HG LncRNA was sponged by these miRNA that was extracted from experimental and predictive DIANA LncBase v.2 modules. As a result, these miRNAs and lncRNAs can act as a ceRNA network which has an effect on KRT31 gene regulation.
Conclusion: In summary, this finding could be suggested novel interactions among lncRNA, mRNA, and miRNA (MIR497HG, KRT31, hsa-miR-4766-3p) for the candidate diagnostic and prognostic markers associated with SKCM by bioinformatics analysis. We believe that, without any severe negative side effects, this ceRNA network could be used as a potential tool for both preventative and adjuvant treatment techniques in SKCM patients.