1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Rs78293998 promotes the hepatocellular carcinoma by disturbing the folding and interaction of CDKN3 protein: integrated gene expression and proteomics analyses
Paper ID : 1461-ICB10
Authors:
Benyamin Mashhadi1, Mohammad Rezaei1, Mansoureh Azadeh *1, Pegah Javid2
1Zist Fanavari Novin Biotechnology Institute
2zist fanavari novin biotechnology institue
Abstract:
Hepatocellular carcinoma (HCC) is now one of the most common cancers and the top cause of cancer-related death worldwide [1]. This investigation aimed to find a novel differentially expressed gene (DEG) in the HCC patients compared to control samples. Expression analysis of GSE121248 achieved from GEO2R online software and validation of expression analyses performed by GEPIA2 [2] database. Single nucleotide polymorphisms (SNPs) of CDKN3 extracted from dbSNP and identification of deleterious SNPs Brought out from SIFT [3] and PROVEAN [4] databases. Biophysical validation of deleterious SNPs realized from HOPE software [5]. Based on microarray analysis, CDKN3 have a significant up-regulation in the HCC samples, compared to control (logFC: 2.237, p-value < 0.0001). From all of the extracted SNPs on the coding region, SIFT and PROVEAN online software revealed that rs78293998 is the most significant deleterious SNP in the protein-coding region CDKN3. This SNP is the arginine mutation into Isoleucine at the 72nd position of CDKN3 protein based on HOPE software. This mutation is located in the Tyrosine-protein phosphatase domain and can disturb this function of CDKN3 protein. Based on the biophysical validation of HOPE, the mutant residue has less charge and smaller size, which can lead the protein to the loss of main interactions. Furthermore, the mutant residue is more hydrophobic than the wild one, which can result in loss of hydrogen bonds and correct protein folding of CDKN3. In conclusion, rs78293998 can promote the HCC development by changing the expression level of CDKN3 while changing the correct folding and protein interactions of CDKN3 and miss-regulation of Tyrosine-protein phosphatase activity.
Keywords:
Microarray; Data analysis; Protein structure; Single nucleotide variations
Status : Paper Accepted (Poster Presentation)