Zafar Abbas Shah1 and Asima Tayyeb2*
1Department of Bioinformatics, Hazara University Mansehra, Pakistan
2Department of Biological Sciences, University of the Punjab, Pakistan
Liver hepatocellular carcinoma has diverse nature on molecular grounds due to its multidimensional physiology. Cytochrome P450 family has universal driver of various metabolic and regulatory functions in liver. Aim of the current study is to access the role of extra-hepatic CYP1A1 protein mediated pathway in liver malignancy development. For this purpose, novel insilico 3-multi-layered protocol has been designed for extensive identification of drug targets of pathway responsible for tumorigenesis. STRING database (www.string-db.org)has been used for retrieval of CYP1A1 mediated pathway of high confidence score and construct functionally associated clusters. WebGestalt toolkit (www.webgestalt.com)for gene enrichment and characterization analysis of CYP1A1 network was carried out. Finally, using cBioPortal (www.cbioportal.org), a cancer genome protocol for analysis of CYP1A1 pathway contribution in liver carcinoma was also performed. Results identified more than 45 proteins (AHR, EPHX1, GSTP1, HPGDS, UGT1A6, GST1, HELZ2, NCOA2, CREBBP, TBL1XR1, RXRA, PPARA, TP53, RB1, BCL9, CCNE2, HSF1, SNRPE, ARID1A, PYGO2 and Histone family) that have unique interactions which play comprehensive role in progression of carcinoma. Identified proteins were proposed as a drug co-targets for advanced personalized therapy. Moreover, this study provides a repository of drug markers in context of CYP1A1 mediated signaling in liver carcinoma. It also opens window for further research to characterize the binding sites, interaction sites, signaling flow quantification and drug designing to break these interactions for better survival.
CYP1A1; Hepatocellular carcinoma; Bioinformatics
Shah ZA, Tayyeb A. Insilico Investigation of CYP1A1 Mediated Pathway Contribution in Liver Hepatocellular Carcinoma: A Drug Discovery Approach. Annals Stem Cell Regenerat Med. 2018; 1(2): 1010.