SEMA6A-AS1/miR-148a-5p/RYR2 ceRNA axis regulates the insulin secretion signaling pathway in cancerous renal patients: integrated bioinformatics and systems biology investigation
SEMA6A-AS1/miR-148a-5p/RYR2 ceRNA axis regulates the insulin secretion signaling pathway in cancerous renal patients: integrated bioinformatics and systems biology investigation
Sahar Kamran,1Mohammad Rezaei,2Mansoureh Azadeh,3,*
1. Zist Fanavari Novin Biotechnology Institute 2. Zist Fanavari Novin Biotechnology Institute 3. Zist Fanavari Novin Biotechnology Institute
Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, comprising approximately 75% of all kidney tumors.[1]. This investigation aimed to find a novel differentially expressed gene (DEG) in the ccRCC patients compared to control samples.
Methods: Initially, gene expression data of ccRCC patients (GSE168845) was obtained from the NCBI Gene Expression Omnibus (GEO) and then analyzed by GEO2R to find differentially expressed genes (DEGs). A gene was selected for further study. Survival and expression were performed by GEPIA2[2] and ENCORI[3]. gene ontology information and biological pathway involvement were understood by using Enrichr[4], KEGG[5], and GENECARDS[6]. RYR2 was taken to miRWalk[7] to find miRNA. miRNA was searched in LncBase v.3 [8], and appropriate lncRNAs were found.
Results: Through analysis of the GEO dataset, a gene named RYR2 was found to be considerably upregulated (|logFC| = 4.24, adj. P value =1.19e-07) in ccRCC samples. RYR2 has a significantly high expression, based on ENCORI (Fold Change: 2.72, FDR: 0.027). The survival has shown that the death rate was higher in people with high expression compared with low expression (Logrank p=3.7e−06, HR(high)=2.1, p(HR)=6e−06). lncRNAs and hsa-miR-148a-5p interaction with RYR2.Analysis of hsa-miR-148a-5p revealed that Increasing the expression of hsa-miR-148a-5p is one of the factors that increase the expression of RYR2. Pathway analysis expressed that RYR2 is involved in the secretion of insulin.
Conclusion: In conclusion, RYR2 is overexpressed in ccRCC and forms a possible ceRNA network. SEMA6A-AS1 by regulating the expression of RYR2 indirectly can work as a ceRNA and it can affect insulin secretion.