Down-regulation of HSD17B13 and the role of rs76926692 as potential factors in development of Liver Hepatocellular Carcinoma: Bioinformatic analysis of proteomics data
Down-regulation of HSD17B13 and the role of rs76926692 as potential factors in development of Liver Hepatocellular Carcinoma: Bioinformatic analysis of proteomics data
Introduction: Liver Hepatocellular Carcinoma (LIHC) is one of the most hazardous cancers. Although many significant breakthroughs have been made in medical treatments, LIHC is one of the most common causes of death universally.
Methods: Expression analysis of GSE136247 was obtained from GEO2R online software, and the GEPIA2 database confirmed expression analysis. After using the mirwalk database, a microRNA was picked up, and its correlation with HSD17B13 was studied. Single nucleotide polymorphism (SNPs) of HSD17B13 acquired from dbSNP and detection of deleterious SNPs from SIFT database. Then, structural modifications of these SNPs were checked in HOPE software in order to recognize the reasons for this harmful effect on the development of LIHC.
Results: According to the microarray analysis, HSD17B13 has a notable down-regulation in the LIHC samples compared to controls. Chose the best-interacted miRNA, which was hsa-miR-7974 with HSD17B13. Moreover, after performing a correlation analysis between these two applying Encori, the result obtained from 370 samples of LIHC supported the previous finding that hsa-miR-7974 down-regulates HSD17B13 in this disease due to the convincing R=-0.201 and p-value=9.86e-05. Based on the Reactome database, HSD17B13 plays a role in numerous signaling pathways associated with LIHC, such as MAPK family signaling cascades, Receptor Tyrosine Kinases, and Hedgehog. The down-regulation of HSD17B13, which has oxidoreductase activity, involves the progression of LIHC. Among plenty of deleterious SNPs in the coding region of HSD17B13, rs76926692 is one of the most significant deleterious ones. In this SNP, Proline residue mutates to Glutamine at position 260. This mutant residue is larger and can't fit the protein core, which may cause a problem in the binding process, and less hydrophobicity, which causes hydrophobic interactions deficiency which can cause a problem in folding correctly. Furthermore, since this mutation happened at the highly conserved residue, it is likely to have a devastating effect on the protein.
Conclusion: In conclusion, several pieces of evidence were in agreement with the down-regulation of HSD17B13 in LIHC, and rs76926692 can encourage the development of LIHC by modifying the folding and the interactions of this protein.
Keywords: Liver Hepatocellular Carcinoma, Single nucleotide variations, Microarray, Data analysis