Role of Resistin Mutations in Chemotherapy Resistance: A Computational Analysis in Iraqi Women with Breast Cancer

Authors

DOI:

https://doi.org/10.32007/jfacmedbaghdad3148

Keywords:

Breast cancer, Resistin, haploreg, swissmodel, in silico

Abstract

Introduction: Breast cancer is one of the most common types of cancer diagnosed in women, and there are multiple genetic and environmental causes involved in progression of this type of cancer. Methods: The study aimed to analyses some Single Nucleotide Polymorphisms (SNPs) that are harmful to the structure and function of Resistin (RETN) protein which is the target for chemotherapy in breast cancer.  We employed a variety of computational methodologies to find SNPs that are harmful to the structure and function of the RETN protein and could cause chemoresistance in breast cancer patients. Haploreg, Regulome DB, Poly- Phen-2, Protparam, and SWISS-MODEL were among the in-silico methods used to do the computational research. Results: The findings reveal that mutations of rs1862513, rs3219175, rs34788323 and rs3745367 are important alterations in native RETN protein that may contribute to its chemoresistance and, ultimately, breast cancer. The study also provided three-dimensional structures of the native and mutant model of RETN protein. Conclusion: According to our results of in silico analysis, these SNPs may have an effect on the binding site of some transcription factors (TFs) which may attribute to the nature of transcription factors that could be affected by others TFs and activators.

References

1. Alkashaf KH, Mohammed SI. Impact of Clinical Pharmacist Intervention on Chemotherapy Knowledge, Attitude, and Practice among Breast Cancer Women. J Fac Med Baghdad. 2024 Apr 1;66(1):103-9. https://doi.org/10.32007/jfacmedbagdad.6612221.

2. Alhadethy DM, Altameemi EK, Khalaf LA, Kamal AM. Pathological Nipple discharge: a comparison between breast ultrasound and mammography. J Fac Med Baghdad. 2021 May 11;63(1):18-23. https://doi.org/10.32007/jfacmedbagdad.6311813.

3. Jasim SS, Taha GI. Comparison between HSV-1 Ag detection techniques by ELISA and real-time PCR in breast cancer patients suffering from periodontitis. J Fac Med Baghdad. 2023 Oct 1;65(3):227-33. https://doi.org/10.32007/jfacmedbagdad.2105.

4. Muñoz-Palomeque A, Guerrero-Ramirez MA, Rubio-Chavez LA, Rosales-Gomez RC, Lopez-Cardona MG, Barajas-Avila VH, et al. Association of RETN and CAP1 SNPs, expression and serum resistin levels with breast cancer in Mexican women. Genetic testing and molecular biomarkers. 2018 Apr 1;22(4):209-17. https://doi.org/10.1089/gtmb.2017.0212.

5. Sahan KA, Aziz IH, Dawood SN, Al Qazzaz H. The role of resistin gene polymorphism in Iraqi breast cancer patients. Biomedicine. 2022 Dec 31;42(6):1296-300. https://doi.org/10.51248/.v42i6.2393.

6. Aziz MA, Akter T, Sarwar MS, Islam MS. The first combined meta‐analytic approach for elucidating the relationship of circulating resistin levels and RETN gene polymorphisms with colorectal and breast cancer. EJMHG. 2022 Mar 1;23(1):27. https://doi.org/10.1186/s43042-022-00240-w.

7. Farhan HM, Abougabal K, Ramadan ME, Darwish T, Eldeiry NA, Abdelkareem SA. Impacts of RETN genetic polymorphism on breast cancer development in Beni-Suef females, Egypt. Egypt. J. Immunol. 2023 Apr;30:37-46. https://doi.org/10.55133/eji.300204.

8. Elkhattabi L, Morjane I, Charoute H, Saile R, Barakat A. Computational screening and analysis of the functional and structural impact of SNPS of the human RETN gene associated to type 2 diabetes. Atherosclerosis. 2020 Dec 1;315:e199-200. https://doi.org/10.1016/j.atherosclerosis.2020.10.622.

9. PolyPhen-2. [2023 Jan 10]. Retrieved from http://genetics.bwh.harvard.edu/pph2.

10. Haploreg. [2023 Jan 10]. Retrieved from https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php.

11. SNPinfo. [2023 Jan 10]. National Institute of Environmental Health Sciences. Retrieved from https://snpinfo.niehs.nih.gov/.

12. RegulomeDB. [2023 Jan 10]. Retrieved from https://regulomedb.org/regulome-search/.

13. ExPASy. [2023 Jan 10]. Retrieved from http://www.expasy.org/.

14. Swiss-Model. [2023 Jan 10]. Retrieved from https://swissmodel.expasy.org/.

15. Deb A, Deshmukh B, Ramteke P, Bhati FK, Bhat MK. Resistin: A journey from metabolism to cancer. TRANON. 2021 Oct 1;14(10):101178. https://doi.org/10.1016/j.tranon.2021.10.

16. Issac RM, Saldanha P, Mathai JM, Mathews J, Mathews R, Kumari B, et al. Histopathological characterization of carcinoma breast with BRCA1/2 sequence variation in a tertiary care center in Kerala, South India. BBRJ. 2022 Jan 1;6(1):117-21. https://doi.org/10.4103/bbrj.bbrj_206_21.

17. Lu XJ. DSSR-enabled innovative schematics of 3D nucleic acid structures with PyMOL. Nucleic acids research. 2020 Jul 27;48(13):e74-. https://doi.org/10.1093/nar/gkaa426.

18. Capriotti E, Montanucci L, Profiti G, Rossi I, Giannuzzi D, Aresu L, et al.. Fido-SNP: the first webserver for scoring the impact of single nucleotide variants in the dog genome. Nucleic Acids Research. 2019 Jul 2;47(W1):W136-41. https://doi.org/10.1093/nar/gkz420.

19. Mohanta TK, Khan A, Hashem A, Abd_Allah EF, Al-Harrasi A. The molecular mass and isoelectric point of plant proteomes. BMC genomics. 2019 Dec;20:1-4.

https://doi.org/10.1186/s12864-019-5983-8.

20. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al.. SWISS-MODEL: homology modelling of protein structures and complexes. NAR. 2018 Jul 2;46(W1):W296-303. https://doi.org/10.1093/nar/gky427.

21. Sriram N, Mukherjee S, Sah MK. Gene expression profiling and protein-protein interaction analysis reveals the dynamic role of MCM7 in Alzheimer's disorder and breast cancer. 3 Biotech. 2022 Jul;12(7):146. https://doi.org/10.1007/s13205-022-03207-1.

22. Chi LA, Vargas MC. In silico design of peptides as potential ligands to resistin. Journal of molecular modeling. 2020 May;26:1-4. https://doi.org/10.1007/s00894-020-4338-3.

23. Sudan SK, Deshmukh SK, Poosarla T, Holliday NP, Dyess DL, Singh AP, et al.. Resistin: An inflammatory cytokine with multi-faceted roles in cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2020 Dec 1;1874(2):188419. https://doi.org/10.1016/j.bbcan.2020.188419.

24. Sahan KA, Aziz IH, Dawood SN, Abdul Razzaq SS. The Effect of Genetic Polymorphism of Resistin Gene among Iraqi Breast Cancer Women. Iraqi journal of biotechnology. 2023; 22 (1), 1-7. 565-Article Text-881-1-10-20230703.pdf

25. Tripathi D, Kant S, Pandey S, Ehtesham NZ. Resistin in metabolism, inflammation, and disease. The FEBS journal. 2020 Aug;287(15):3141-9. https://doi.org/10.1111/febs.15322.

26. Lim SW, Tan KJ, Azuraidi OM, Sathiya M, Lim EC, Lai KS, Yap WS, Afizan NA. Functional and structural analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the MYB oncoproteins associated with human cancer. Scientific Reports. 2021 Dec 17;11(1):24206. https://doi.org/10.1038/s41598-021-03624-x.

Resistin; Mutations; Chemotherapy; Resistance; Computational; Analysis

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Published

01.10.2025

How to Cite

1.
Sahan KA, Sahan ZA, Turki TG. Role of Resistin Mutations in Chemotherapy Resistance: A Computational Analysis in Iraqi Women with Breast Cancer. J Fac Med Baghdad [Internet]. 2025 Oct. 1 [cited 2025 Oct. 1];67(3):359-67. Available from: https://www.iqjmc.uobaghdad.edu.iq/index.php/19JFacMedBaghdad36/article/view/3148

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