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

Overview

Journal Avicenna J Med Biotechnol

Specialty Biomedical Engineering

Date 2023 Feb 15

PMID 36789117

Authors

Fatemeh Saberi

Zeinab Dehghan

Effat Noori

Zahra Taheri

Marzieh Sameni

Hakimeh Zali

Affiliations

Soon will be listed here.

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 (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 and 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.

Citing Articles

Technetium-99m-methylene diphosphonate single photon emission computed tomography/computed tomography combined with prostate-specific antigen/free prostate-specific antigen ratio for bone metastasis of prostate cancer.

He J, Zhong Y, Zhang S World J Clin Cases. 2024; 12(20):4082-4090.

PMID: 39015893 PMC: 11235539. DOI: 10.12998/wjcc.v12.i20.4082.

Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation.

Moayeri M, Irani S, Novin M, Salahshourifar I, Salehi M Reprod Sci. 2024; 31(10):3112-3121.

PMID: 39014289 DOI: 10.1007/s43032-024-01640-6.

Transcriptome analysis revealed differences in gene expression in sheep muscle tissue at different developmental stages.

Wan S, Lou M, Zhang S, Li S, Ling Y BMC Genom Data. 2024; 25(1):54.

PMID: 38849746 PMC: 11162047. DOI: 10.1186/s12863-024-01235-9.

Deciphering the similarities and disparities of molecular mechanisms behind respiratory epithelium response to HCoV-229E and SARS-CoV-2 and drug repurposing, a systems biology approach.

Dehghan Z, Mirmotalebisohi S, Mozafar M, Sameni M, Saberi F, Derakhshanfar A Daru. 2024; 32(1):215-235.

PMID: 38652363 PMC: 11087451. DOI: 10.1007/s40199-024-00507-0.

Identification of Renal Transplantation Rejection Biomarkers in Blood Using the Systems Biology Approach.

Saberi F, Dehghan Z, Noori E, Zali H Iran Biomed J. 2024; 27(6):375-87.

PMID: 38224029 PMC: 10826908. DOI: 10.52547/ibj.3871.

References

Watabe T, Lin M, Ide H, Donjacour A, Cunha G, Witte O . Growth, regeneration, and tumorigenesis of the prostate activates the PSCA promoter. Proc Natl Acad Sci U S A. 2001; 99(1):401-6. PMC: 117572. DOI: 10.1073/pnas.012574899. View

Hou H, Sun D, Zhang X . The role of amplification and overexpression in therapeutic resistance of malignant tumors. Cancer Cell Int. 2019; 19:216. PMC: 6704499. DOI: 10.1186/s12935-019-0937-4. View

Baron V, Adamson E, Calogero A, Ragona G, Mercola D . The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin. Cancer Gene Ther. 2005; 13(2):115-24. PMC: 2455793. DOI: 10.1038/sj.cgt.7700896. View

Li L, Ameri A, Wang S, Jansson K, Casey O, Yang Q . EGR1 regulates angiogenic and osteoclastogenic factors in prostate cancer and promotes metastasis. Oncogene. 2019; 38(35):6241-6255. PMC: 6715537. DOI: 10.1038/s41388-019-0873-8. View

Zachariou M, Minadakis G, Oulas A, Afxenti S, Spyrou G . Integrating multi-source information on a single network to detect disease-related clusters of molecular mechanisms. J Proteomics. 2018; 188:15-29. DOI: 10.1016/j.jprot.2018.03.009. View

Ravindran F, Jain A, Desai S, Menon N, Srivastava K, Bawa P . Whole-exome sequencing of Indian prostate cancer reveals a novel therapeutic target: POLQ. J Cancer Res Clin Oncol. 2022; 149(6):2451-2462. DOI: 10.1007/s00432-022-04111-0. View

Ahnert S, Fink T . Form and function in gene regulatory networks: the structure of network motifs determines fundamental properties of their dynamical state space. J R Soc Interface. 2016; 13(120). PMC: 4971217. DOI: 10.1098/rsif.2016.0179. View

Smith-Palmer J, Takizawa C, Valentine W . Literature review of the burden of prostate cancer in Germany, France, the United Kingdom and Canada. BMC Urol. 2019; 19(1):19. PMC: 6421711. DOI: 10.1186/s12894-019-0448-6. View

Mamede A, Abrantes A, Pedrosa L, Casalta-Lopes J, Pires A, Teixo R . Beyond the limits of oxygen: effects of hypoxia in a hormone-independent prostate cancer cell line. ISRN Oncol. 2013; 2013:918207. PMC: 3791829. DOI: 10.1155/2013/918207. View

10.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

11.

Dehghan Z, Mohammadi-Yeganeh S, Sameni M, Mirmotalebisohi S, Zali H, Salehi M . Repurposing new drug candidates and identifying crucial molecules underlying PCOS Pathogenesis Based On Bioinformatics Analysis. Daru. 2021; 29(2):353-366. PMC: 8416576. DOI: 10.1007/s40199-021-00413-9. View

12.

Jiramongkol Y, Lam E . FOXO transcription factor family in cancer and metastasis. Cancer Metastasis Rev. 2020; 39(3):681-709. PMC: 7497309. DOI: 10.1007/s10555-020-09883-w. View

13.

Zhang Q, Huang H, Liu A, Li J, Liu C, Sun B . Cell division cycle 20 (CDC20) drives prostate cancer progression via stabilization of β-catenin in cancer stem-like cells. EBioMedicine. 2019; 42:397-407. PMC: 6491421. DOI: 10.1016/j.ebiom.2019.03.032. View

14.

Huang H, Lin Y, Li J, Huang K, Shrestha S, Hong H . miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database. Nucleic Acids Res. 2019; 48(D1):D148-D154. PMC: 7145596. DOI: 10.1093/nar/gkz896. View

15.

Liao Y, Wang J, Jaehnig E, Shi Z, Zhang B . WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019; 47(W1):W199-W205. PMC: 6602449. DOI: 10.1093/nar/gkz401. View

16.

Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M . Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016. EPMA J. 2016; 7:23. PMC: 5078893. DOI: 10.1186/s13167-016-0072-4. View

17.

Pienta K, Esper P . Risk factors for prostate cancer. Ann Intern Med. 1993; 118(10):793-803. DOI: 10.7326/0003-4819-118-10-199305150-00007. View

18.

Accili D, Arden K . FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell. 2004; 117(4):421-6. DOI: 10.1016/s0092-8674(04)00452-0. View

19.

Schwartz G . Prostate cancer, serum parathyroid hormone, and the progression of skeletal metastases. Cancer Epidemiol Biomarkers Prev. 2008; 17(3):478-83. DOI: 10.1158/1055-9965.EPI-07-2747. View

20.

Levrier C, Rockstroh A, Gabrielli B, Kavallaris M, Lehman M, Davis R . Discovery of thalicthuberine as a novel antimitotic agent from nature that disrupts microtubule dynamics and induces apoptosis in prostate cancer cells. Cell Cycle. 2017; 17(5):652-668. PMC: 5976206. DOI: 10.1080/15384101.2017.1356512. View