همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

BIRC5: The Silent Architect of Tumor Persistence and Senescence in Hepatocellular Carcinoma

نویسندگان :

Amirhosein Farrokhzad¹ Maryam Kaboli² Elahe Hoseinnia³ Elham Rismani⁴ Massoud Vosough⁵

1- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran Department of Molecular Cell Biology-Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran 2- Department of Molecular Cell Biology-Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 3- Department of Biotechnology, Alzahra University, Tehran, Iran 4- Molecular Medicine Department, Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran 5- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran

کلمات کلیدی :

liver cancer،molecular targeted therapy،aging،BIRC5،structural bioinformatics

چکیده :

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 [Hajilou and Solhi,2024]. 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 [Zhang and Zheng,2023]. 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 GSE60502, GSE112790 and GSE14520 were obtained from the GEO database. DEGs were obtained using R packages and screened out according to adjusted P-value < 0.05 and -logFC- ≥1. 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 BIRC5 because of its expression pattern and level of expression in normal liver. BIRC5 (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 BIRC5 or blocking the antiapoptotic pathway significantly increases cell death in response to TNFα [Li and Fu,2016]. One active compound that targets the BIRC5 is Tiliroside, a natural flavonoid glycoside, which is a promising candidate compound [Grochowski and Locatelli,2018]. 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 [Yang and Lu,2023]. Finally, we performed a molecular docking analysis to investigate the binding affinity between this compound and BIRC5 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 (https://plip-tool.biotec.tu-dresden.de/plip-web/plip/index) was used to analyze hydrogen bonds and hydrophobic interactions. The molecular docking studies confirmed the strong interaction between Tiliroside and BIRC5 and presented evidence for its therapeutic potential as a new agent targeting BIRC5 for HCC. In conclusion, targeting BIRC5 by Tiliroside could be a potential therapeutic approach for HCC treatment