[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit ::
Main Menu
Home::
Journal Information::
Articles Archive::
Guide for Authors::
For Reviewers::
Ethical Statements::
Registration::
Site Facilities::
Contact us::
::
Indexed by
     
..
Search in website

Advanced Search
..
Receive site information
Enter your Email in the following box to receive the site news and information.
..
Copyright Policies

 

AWT IMAGE

 

..
Open Access Policy

This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

..
:: Articles In Press ::
Back to the articles list Back to browse issues page
Identifying Mechanisms of Radiation Resistance in Glioblastoma Using Bioinformatic and Molecular-Cellular Approaches
Arezou Eshaghadadi , Taereh Foroutan * , Ali Gorji , Noormohammad Meshkinkhood
Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran , foroutan@khu.ac.ir
Abstract:   (38 Views)
Introduction: Glioblastoma (GBM) represents the most common and aggressive malignant brain tumor in adults, characterized by poor responsiveness to both radiotherapy and chemotherapy. The average survival duration for affected patients ranges from 14 to 20 months. This study aims to elucidate the molecular underpinnings of radiation resistance in GBM by integrating bioinformatic analyses with experimental laboratory approaches. Materials and Methods: Analysis of gene expression datasets identified four candidate genes (KLF10, THBS1, NFYB, OSR1). Human GBM cells were cultured, irradiated with 6 Gy, and processed for RNA isolation and qPCR to evaluate gene expression. Results: Our results showed that OSR1 expression was significantly increased, while THBS1 levels were decreased in radiation-resistant cells compared to control samples; however, KLF10 and NFYB did not exhibit significant changes. Conclusion: These findings implicate OSR1 and THBS1 as potential biomarkers of radiation resistance. Further investigations into their pathways could help in developing targeted therapies for GBM.
 
Keywords: Glioma, Cell Culture Techniques, Computational Biology, Genes
Full-Text [PDF 2586 kb]   (18 Downloads)    
Type of Study: Research --- Open Access, CC-BY-NC | Subject: Molecular Neurobiology
References
1. Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LA, Eheman C, et al. Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst. 2011; 103(9): 714-36. [DOI:10.1093/jnci/djr077]
2. Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015; 314(23): 2535-43. [DOI:10.1001/jama.2015.16669]
3. Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10): 987-96. [DOI:10.1056/NEJMoa043330]
4. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014; 370(8): 699-708. [DOI:10.1056/NEJMoa1308573]
5. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014; 370(8): 709-22. [DOI:10.1056/NEJMoa1308345]
6. Chédeville AL, Madureira PA. The role of hypoxia in glioblastoma radiotherapy resistance. Cancers. 2021; 13(3): 542. [DOI:10.3390/cancers13030542]
7. Ali MY, Oliva CR, Noman ASM, Allen BG, Goswami PC, Zakharia Y, et al. Radioresistance in glioblastoma and the development of radiosensitizers. Cancers. 2020; 12(9): 2511. [DOI:10.3390/cancers12092511]
8. Li H-F, Kim J-S, Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat Oncol. 2009; 4: 43. [DOI:10.1186/1748-717X-4-43]
9. Kim Y, Kim KH, Lee J, Lee Y, Kim M, Lee SJ, et al. Wnt activation is implicated in glioblastoma radioresistance. Lab Invest. 2012; 92(3): 466-73. [DOI:10.1038/labinvest.2011.161]
10. Papavassiliou KA, Papavassiliou AG. Transcription factors in glioblastoma-molecular pathogenesis and clinical implications. Biochim Biophys Acta Rev Cancer. 2022; 1877(1): 188667. [DOI:10.1016/j.bbcan.2021.188667]
11. Dahan P, Martinez Gala J, Delmas C, Monferran S, Malric L, Zentkowski D, et al. Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance. Cell Death Dis. 2014; 5(11): e1543. [DOI:10.1038/cddis.2014.509]
12. Bache M, Zschornak MP, Passin S, Keßler J, Wichmann H, Kappler M, et al. Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions. Radiat Oncol. 2011; 6: 111. [DOI:10.1186/1748-717X-6-111]
13. Wu W, Klockow JL, Zhang M, Lafortune F, Chang E, Jin L, et al. Glioblastoma multiforme (GBM): an overview of current therapies and mechanisms of resistance. Pharmacol Res. 2021; 171: 105780. [DOI:10.1016/j.phrs.2021.105780]
14. Liao K, Ma X, Chen B, Lu X, Hu Y, Lin Y, et al. Upregulated AHIF-mediated radioresistance in glioblastoma. Biochem Biophys Res Commun. 2019; 509(2): 617-23. [DOI:10.1016/j.bbrc.2018.12.136]
15. Zheng R, Yao Q, Ren C, Liu Y, Yang H, Xie G, et al. Upregulation of long noncoding RNA small nucleolar RNA host gene 18 promotes radioresistance of glioma by repressing semaphorin 5A. Int J Radiat Oncol Biol Phys. 2016; 96(4): 877-87. [DOI:10.1016/j.ijrobp.2016.07.036]
16. Brodie S, Lee HK, Jiang W, Cazacu S, Xiang C, Poisson LM, et al. The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells. Oncotarget. 2017; 8(19): 31785-801. [DOI:10.18632/oncotarget.15991]
17. Memon A, Lee WK. KLF10 as a tumor suppressor gene and its TGF-β signaling. Cancers. 2018;10(6):161. [DOI:10.3390/cancers10060161]
18. Subramaniam M, Hawse JR, Rajamannan NM, Ingle JN, Spelsberg TC. Functional role of KLF10 in multiple disease processes. Biofactors. 2010; 36(1): 8-18. [DOI:10.1002/biof.67]
19. Daubon T, Léon C, Clarke K, Andrique L, Salabert L, Darbo E, et al. Deciphering the complex role of thrombospondin-1 in glioblastoma development. Nat Commun. 2019; 10(1): 1146. [DOI:10.1038/s41467-019-08480-y]
20. Qi C, Lei L, Hu J, Wang G, Liu J, Ou S. Thrombospondin-1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma. Oncol Lett. 2021; 21(1): 22. [DOI:10.3892/ol.2020.12283]
21. Lu T, Li C, Xiang C, Gong Y, Peng W, Hou F, et al. Over-expression of NFYB affects stromal cells reprogramming and predicts worse survival in gastric cancer patients. Aging (Albany NY). 2022; 14(19): 7851-67. [DOI:10.18632/aging.204294]
22. Yu Z, Ouyang L. OSR1 downregulation indicates an unfavorable prognosis and activates the NF-κB pathway in ovarian cancer. Discover Oncology. 2023; 14(1): 159. [DOI:10.1007/s12672-023-00778-0]
23. Chen W, Zou A, Zhang H, Fu X, Yao F, Yang A. Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-κB pathway. Eur J Pharmacol. 2018; 839: 33-9. [DOI:10.1016/j.ejphar.2018.09.020]
24. Zhang Y, Yuan Y, Liang P, Guo X, Ying Y, Shu X-S, et al. OSR1 is a novel epigenetic silenced tumor suppressor regulating invasion and proliferation in renal cell carcinoma. Oncotarget. 2017; 8(18): 30008-18. [DOI:10.18632/oncotarget.15611]
25. Wang Y, Lei L, Xu F, Xu H-T. Reduced expression of odd-skipped related transcription factor 1 promotes proliferation and invasion of breast cancer cells and indicates poor patient prognosis. Oncol Lett. 2020; 20(3): 2946-54. [DOI:10.3892/ol.2020.11820]
26. Chen, WL, Wang, CC, Lin, YJ. Cycling hypoxia induces chemoresistance through the activation of reactive oxygen species-mediated B-cell lymphoma extra-long pathway in glioblastoma multiforme. 2015; 13: 389. [DOI:10.1186/s12967-015-0758-8]
27. Lin W, Wu S, Chen X, Ye Y, Weng Y, Pan Y, Chen Z, Chen L, Qiu X and Qiu S. Characterization of Hypoxia Signature to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Glioma Groups. Front. Oncol. 2020; 10: 796. [DOI:10.3389/fonc.2020.00796]
28. L. Oliver, C. Olivier, F. B. Marhuenda, M. Campone, F. M. Vallette, Hypoxia and the Malignant Glioma Microenvironment: Regulation and Implications for Therapy, Current Molecular Pharmacology; Volume 2, Issue 3, Year 2009; 263-284. [DOI:10.2174/1874467210902030263]
29. Pouyan, A., Ghorbanlo, M., Eslami, M. Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies.2025; 24: 25. [DOI:10.1186/s12943-025-02267-0]
30. Ding Y, et al. CRISPR-based functional genomics identifies OSR1 in PI3K/AKT pathway regulation. Cell Rep. 2024; 42(2): 112154.
31. Uzzaman A, Zhang X, Qiao Z, Zhan H, Sohail A, Wahid A, et al. Discovery of small extracellular vesicle proteins from human serum for liver cirrhosis and liver cancer. Biochimie. 2020; 177: 132-41. [DOI:10.1016/j.biochi.2020.08.013]
32. Li Y, Qin J, Chen G, Liu J, Lin Y, Wang Y, et al. Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer. Int J Clin Oncol. 2024; 29(4): 427-41. [DOI:10.1007/s10147-024-02472-9]
33. Tang Y-F, Wang Y-Z, Wen G-B, Jiang J-J. Prognostic model of kidney renal clear cell carcinoma using aging-related long noncoding RNA signatures identifies THBS1-IT1 as a potential prognostic biomarker for multiple cancers. Aging (Albany NY). 2023; 15(17): 8630-49. [DOI:10.18632/aging.204949]
34. Kaur S, Bronson SM, Pal-Nath D, Miller TW, Soto-Pantoja DR, Roberts DD. Functions of Thrombospondin-1 in the Tumor Microenvironment. International Journal of Molecular Sciences. 2021; 22(9): 4570. [DOI:10.3390/ijms22094570]
35. Whitehead CA, Morokoff AP, Kaye AH, Drummond KJ, Mantamadiotis T, Stylli SS. Invadopodia associated thrombospondin-1 contributes to a post-therapy pro-invasive response in glioblastoma cells. Exp Cell Res. 2023; 431(1): 113743. [DOI:10.1016/j.yexcr.2023.113743]
36. Guo, W-F., Lin, R-X., Huang, J., Zhou, Z., Yang, J., Guo, G-Z. and Wang, S-Q. Identification of Differentially Expressed Genes Contributing to Radioresistance in Lung Cancer Cells using Microarray Analysis. Radiat. Res. 2005; 164(1): 27-35. [DOI:10.1667/RR3401]
37. Michna, A., Schötz, U., Selmansberger, M. et al. Transcriptomic analyses of the radiation response in head and neck squamous cell carcinoma subclones with different radiation sensitivity: time-course gene expression profiles and gene association networks. 2016; 11: 94 [DOI:10.1186/s13014-016-0672-0]
38. Jun Guo, Anahita Fathi Kazerooni, Hamed Akbari, Erik Toorens, Chiharu Sako, elizabeth mamourian, constantinos koumenis, stephen bagley, zev a binder, robert lustig, donald o'rourke, tapan ganguly, spyridon bakas, maclean nasrallah, christos davatzikos, nimg-37. joint learning of imaging and genomic data reveals distinct glioblastoma subtypes, Neuro-Oncology, Volume 24, Issue Supplement_7, November 2022, Page vii171. [DOI:10.1093/neuonc/noac209.655]
39. Mohammad Fayyad Zaman, Marc Daou, Lynette M Phillips, Sanjay Singh, Lihong Long, Joy Gumin, Daniel Ledbetter, Frederick F Lang, tmic-46. transcriptional heterogeneity and mechanistic pathways of recurrent glioblastoma: insights from a pre-clinical recurrent tumor model, Neuro-Oncology, Volume 26, Issue Supplement_8, November 2024. [DOI:10.1093/neuonc/noae165.1224]
40. Liu P, Xing N, Xiahou Z, Yan J, Lin Z, Zhang J. Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level. Front Immunol. 2024; 15: 1368685. [DOI:10.3389/fimmu.2024.1368685]
41. Choi J, Kim G, Cho SB, Im H-J. Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme. J Nanobiotechnology. 2020; 18(1): 122. [DOI:10.1186/s12951-020-00684-5]
42. Khabibov M, Garifullin A, Boumber Y, Khaddour K, Fernandez M, Khamitov F, et al. Signaling pathways and therapeutic approaches in glioblastoma multiforme. Int J Oncol. 2022; 60(6): 69. [DOI:10.3892/ijo.2022.5359]
43. Ou A, Yung WA, Majd N. Molecular mechanisms of treatment resistance in glioblastoma. Int J Mol Sci. 2021; 22(1): 351. [DOI:10.3390/ijms22010351]
44. Stanzani E, Martínez-Soler F, Mateos T. Martín, Vidal N, Villanueva A, Pujana M. Angel, Serra-Musach J., de la Iglesia N., Giménez-Bonafé P., Tortosa A. Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program. Oncotarget. 2017; 8: 73640-73653. [DOI:10.18632/oncotarget.18363]
45. Georg Emons; Melanie Spitzner; Sebastian Reineke; Janneke Möller; Noam Auslander; Frank Kramer, et al. Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling. Mol Cancer Res 2017; 15(11): 1481-1490. [DOI:10.1158/1541-7786.MCR-17-0205]
46. Masoumeh Eliyasi Dashtaki, Elham Karimi, Sorayya Ghasemi. Genetic Variants Impacting Angiogenesis Signaling Pathways in Glioblastoma Multiforme: A Systematic Review of Mutations and Polymorphisms. Current Molecular Medicine, 2024; 11: 1346-1357. [DOI:10.2174/1566524023666230725115812]
47. Yin, J, Ding, F, Cheng, Z. METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling. 2023; 14: 417(2023). [DOI:10.1038/s41419-023-05933-7]
48. Xue, C., Chu, Q., Shi, Q. et al. Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.2025; 10: 106. [DOI:10.1038/s41392-025-02142-w]
49. Mahmood T, Yang PC. Western blot: technique, theory, and trouble shooting. N Am J Med Sci. 2018; 10(9): 671-7.
50. Moffitt JR, Lundberg E, Heyn H. The emerging landscape of spatial profiling technologies. Nat Rev Genet. 2022; 23(12): 741-59. [DOI:10.1038/s41576-022-00515-3]
51. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2018; 173(1): 20-51. [DOI:10.1016/j.cell.2018.03.006]
52. Sprooten J, Vankerckhoven A, Vanmeerbeek I, Borras DM, Berckmans Y, Wouters R, et al. Peripherally driven myeloid NFkB and IFN/ISG responses predict malignancy risk, survival, and immunotherapy regime in ovarian cancer. J Immunother Cancer. 2021; 9(11): e003609. [DOI:10.1136/jitc-2021-003609]
53. Derynck R, Turley SJ, Akhurst RJ. TGFβ biology in cancer progression and immunotherapy. Nat Rev Clin Oncol. 2021; 18(1): 9-34. [DOI:10.1038/s41571-020-0403-1]
54. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018; 18(5): 309-24. [DOI:10.1038/nri.2017.142]
55. Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ, et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell. 2019; 178(4): 835-49.e21. [DOI:10.1016/j.cell.2019.06.024]


XML   Persian Abstract   Print



Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Back to the articles list Back to browse issues page
مجله علوم اعصاب شفای خاتم The Neuroscience Journal of Shefaye Khatam
Persian site map - English site map - Created in 0.05 seconds with 45 queries by YEKTAWEB 4732