Up-regulation of PSAT1 in colorectal cancer patients regulates by a novel ceRNA network: an integrated systems biology approach
Up-regulation of PSAT1 in colorectal cancer patients regulates by a novel ceRNA network: an integrated systems biology approach
Maryam Shakarami,1Mohammad Rezaei,2Mansoureh Azadeh,3,*
1. Zist Fanavari Novin Biotechnology Institute 2. Zist Fanavari Novin Biotechnology Institute 3. Zist Fanavari Novin Biotechnology Institute
Introduction: Colorectal cancer (CRC), ranking second most commonly diagnosed cancer and the third most common cancer related to death in the world. CRC is divided into 72% colon carcinoma and 28% rectum cancer, though the occurrence of CRC is sometimes related together. it's for the most part considered a genetic disease, which is characterized by a continuous accumulation of genetic changes. In line with recent studies, numerous risk factors can cause CRC, among these, genetic biomarkers are considered to possess a basic impact on the progress of CRC.
Therefore, extensively bioinformatics analysis has been utilized in order to determine these biomarkers as targets for the treatment of CRC.
Methods: At the outset, NCBI Gene Expression Omnibus (GEO) was elected to get the desired GSE (GSE9348), and therefore the gene expression profile (Fig 4) was analyzed by R Studio to search out differentially expressed genes in CRC tissue compared to controls (Fig 5), so the PSAT1 was selected for further studies. The pathways which are related to the PSAT1 gene (Fig 8 – Fig 10) were selected from Reactome pathway database.
Then, to pick out various target PSAT1’s miRNAs, the Free Online prediction software miRWalk 3.0 was utilized, and the experimental and predictive DIANA LncBase V.2 modules were used to identify the LncRNA list that targeted by miRNAs. Ultimately, the analysis of the pathways concerned in CRC were determined the ceRNAs as one of the post-transcription regulators.
Results: According to GEO analysis of GSE9348 were indicated 13658 up and down regulated genes(Fig 6). Among all these genes PSAT1 was considered as a Up-regulated gene that related to CRC and also serine, threonine, cysteine, methionine, vitamin B6 and carbon metabolism, and biosynthesis of amino acids and cofactors pathways (revealed by KEGG). And miRNAs related to PSAT1 were determined by using the Free Online prediction software miRWalk 3.0 Including hsa-miR-548l, hsa-miR-559, hsa-miR-892a, hsa-miR-5195-3p, hsa-miR-302c-5p. lncRNAs sponge attach to their miRNAs targets and were able to change their expression level therefore these lncRNAs were differentiated with the experimental and predictive DIANA LncBase V.2 modules (PWAR6, SMC2-AS1, SPATA41, TMEM191A, SRP14-AS ).
Conclusion: As a result of this study, concluded that PWAR6, SMC2-AS1, SPATA41, TMEM191A, and SRP14-AS lncRNAs act as a tumor suppressor in CRC by inhibiting the function of the hsa-miR-548l, hsa-miR-559, hsa-miR-892a, hsa-miR-5195-3p, hsa-miR-302c-5p miRNAs, so it blocks miRNAs sponging and eventually represses the PSAT1 gene which is an important gene for metabolism and biosynthesis. Therefore, this result may be considered as a potential therapeutic purpose for CRC patients .