The most common and malignant type of
liver cancer is hepatocellular carcinoma (HCC). Due to the lack of early diagnosis methods, people with HCC usually face limited treatment options and poor prognosis. Cellular senescence is a permanent state where cells irreversibly exit the cell cycle and lose their ability to proliferate due to continuous stress-induced damage. Aging and stressors like oxidative stress or oncogene activation cause several liver changes, including reduced size and number of normal hepatocytes, decreased regenerative and metabolic capacity, and an increased proportion of polyploid and multinucleated hepatocytes. Initially, the present study aimed to identify differentially expressed genes (DEGs) between tumor and normal tissues from HCC samples and compare with senescence-associated genes to find hub genes that have been involved in both hepatocarcinogenesis and senescence. Raw microarray data of GSE۶۰۵۰۲, GSE۱۱۲۷۹۰ and GSE۱۴۵۲۰ were obtained from the GEO database. DEGs were obtained using R packages and screened out according to adjusted P-value < ۰.۰۵ and -logFC - ≥۱. Senescence-associated genes file was taken from the CELLAGE database. First, common genes between the senescence-associated genes and DEGs were collected. Then, the hub genes were identified; these genes have function in cancer and also in senescence. The expression patterns were obtained from GEPIA and UALCAN databases and the expression patterns of normal tissue were obtained from HUMAN PROTEIN ATLAS (HPA) and Gtex databases. Among these genes, we focused on
BIRC۵ because of its expression pattern and level of expression in normal liver.
BIRC۵ (Survivin), the smallest member of the inhibitor of apoptosis proteins (IAPs), is highly expressed in precancerous liver lesions and malignant HCC cells. Senescence triggers HCC regression by inducing the inflammatory cytokine TNFα. Depleting
BIRC۵ or blocking the antiapoptotic pathway significantly increases cell death in response to TNFα. One active compound that targets the
BIRC۵ is Tiliroside, a natural flavonoid glycoside, which is a promising candidate compound. Several pharmacological activities have been reported regarding its antithrombotic activity, antioxidant, hepatoprotective, and anti-inflammatory action. It has also been investigated to understand its anti-cancer potential. Finally, we performed a molecular docking analysis to investigate the binding affinity between this compound and
BIRC۵ protein; After preparing the ligand and receptor molecules, AutoDock Vina was used to conduct molecular docking. The web-based server of Protein-Ligand Interaction Profiler was used to analyze hydrogen bonds and hydrophobic interactions. The molecular docking studies confirmed the strong interaction between Tiliroside and
BIRC۵ and presented evidence for its therapeutic potential as a new agent targeting
BIRC۵ for HCC. In conclusion, targeting
BIRC۵ by Tiliroside could be a potential therapeutic approach for HCC treatment
