Identification of Critical Molecular Factors and Side Effects Underlying the Response  to Thalicthuberine in Prostate Cancer: A Systems Biology Approach

Fatemeh  Saberi; Zeinab  Dehghan; Effat  Noori; Zahra  Taheri; Marzieh  Sameni; Hakimeh  Zali

doi:10.18502/ajmb.v15i1.11425

Fatemeh Saberi Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Zeinab Dehghan Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
Effat Noori Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Zahra Taheri Department of Biology and Biotechnology, Pavia University, Pavia, Italy
Marzieh Sameni Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hakimeh Zali Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ajmb.v15i1.11425

Keywords: Bioinformatics, Computational biology, Gene expression, Gene regulatory networks, Prostate cancer

Abstract

Background: Uncontrolled mitosis of cancer cells and resistance cells to chemotherapy drugs are the challenges of prostate cancer. Thalicthuberine causes a mitotic arrest and a reduction of the effects of drug resistance, resulting in cell death. In this study, we applied bioinformatics and computational biology methods to identify functional pathways and side effects in response to Thalicthuberine in prostate cancer patients.

Methods: Microarray data were retrieved from Gene Expression Omnibus (GEO), and protein-protein interactions and gene regulatory networks were constructed, using the Cytoscape software. The critical genes and molecular mechanisms in response to Thalicthuberine and its side effects were identified, using the Cytoscape software and WebGestalt server, respectively. Finally, GEPIA2 was used to predict the relationship between critical genes and prostate cancer.

Results: The POLQ, EGR1, CDKN1A, FOS, MDM2, CDC20, CCNB1, and CCNB2 were identified as critical genes in response to this drug. The functional mechanisms of Thalicthuberine include a response to oxygen levels, toxic substances and immobilization stress, cell cycle regulation, regeneration, the p53 signaling pathway, the action of the parathyroid hormone, and the FoxO signaling pathway. Besides, the drug has side effects including muscle cramping, abdominal pains, paresthesia, and metabolic diseases.

Conclusion: Our model suggested newly predicted crucial genes, molecular mechanisms, and possible side effects of this drug. However, further studies are required.