High Thioredoxin Domain-Containing Protein 11 Expression Is Associated with Tumour Progression in Glioma
Abstract
:1. Introduction
2. Results
2.1. High TXNDC11 Expression Is Associated with Worse Prognosis
2.2. TXNDC11 Knockdown Inhibits GBM Proliferation and Increases Temozolomide (TMZ) Sensitivity
2.3. TXNDC11 Facilitates Migration and Invasion and Downregulates Apoptosis of GBM Cells
2.4. TXNDC11 Promotes Epithelial-Mesenchymal Transition and Affects Cell Cycle of GBM Cells
2.5. TXNDC11 Knockdown Attenuated the Growth of GBM Cells In Vivo
3. Discussion
4. Materials and Methods
4.1. Sample and Preparation
4.2. Tumour Immunohistochemistry
4.3. Cell Lines and Cell Culture
4.4. Real-Time PCR
4.5. Cell Proliferation Assay
4.6. Migration Assay In Vitro
4.7. Cell Invasion Assay In Vitro
4.8. Transfection
4.9. Western Blotting
4.10. Apoptosis Analysis
4.11. Animal Model
4.12. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ostrom, Q.T.; Patil, N.; Cioffi, G.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013–2017. Neuro-Oncology 2020, 22 (Suppl. S2), iv1–iv96. [Google Scholar] [CrossRef] [PubMed]
- Witthayanuwat, S.; Pesee, M.; Supaadirek, C.; Supakalin, N.; Thamronganantasakul, K.; Krusun, S. Survival Analysis of Glioblastoma Multiforme. Asian Pac. J. Cancer Prev. 2018, 19, 2613–2617. [Google Scholar] [CrossRef] [PubMed]
- Brodbelt, A.; Greenberg, D.; Winters, T.; Williams, M.; Vernon, S.; Collins, V.P. Glioblastoma in England: 2007–2011. Eur. J. Cancer 2015, 51, 533–542. [Google Scholar] [CrossRef] [PubMed]
- Louis, D.N.; Perry, A.; Reifenberger, G.; Von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol. 2016, 131, 803–820. [Google Scholar] [CrossRef]
- Molinaro, A.M.; Taylor, J.W.; Wiencke, J.K.; Wrensch, M.R. Genetic and molecular epidemiology of adult diffuse glioma. Nat. Rev. Neurol. 2019, 15, 405–417. [Google Scholar] [CrossRef]
- Weller, M.; van den Bent, M.; Preusser, M.; Le Rhun, E.; Tonn, J.C.; Minniti, G.; Bendszus, M.; Balana, C.; Chinot, O.; Dirven, L.; et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat. Rev. Clin. Oncol. 2021, 18, 170–186. [Google Scholar] [CrossRef]
- Louis, D.N.; Perry, A.; Wesseling, P.; Brat, D.J.; Cree, I.A.; Figarella-Branger, D.; Hawkins, C.; Ng, H.K.; Pfister, S.M.; Reifenberger, G.; et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro-Oncology 2021, 23, 1231–1251. [Google Scholar] [CrossRef]
- Klughammer, J.; Kiesel, B.; Roetzer, T.; Fortelny, N.; Nemc, A.; Nenning, K.-H.; Furtner, J.; Sheffield, N.C.; Datlinger, P.; Peter, N.; et al. The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space. Nat. Med. 2018, 24, 1611–1624. [Google Scholar] [CrossRef]
- Neftel, C.; Laffy, J.; Filbin, M.G.; Hara, T.; Shore, M.E.; Rahme, G.J.; Richman, A.R.; Silverbush, D.; Shaw, M.L.; Hebert, C.M.; et al. An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. Cell 2019, 178, 835–849.e21. [Google Scholar] [CrossRef]
- Arcella, A.; Limanaqi, F.; Ferese, R.; Biagioni, F.; Oliva, M.A.; Storto, M.; Fanelli, M.; Gambardella, S.; Fornai, F. Dissecting Molecular Features of Gliomas: Genetic Loci and Validated Biomarkers. Int. J. Mol. Sci. 2020, 21, 685. [Google Scholar] [CrossRef]
- Wang, D.; De Deken, X.; Milenkovic, M.; Song, Y.; Pirson, I.; Dumont, J.E.; Miot, F. Identification of a novel partner of duox: EFP1, a thioredoxin-related protein. J. Biol. Chem. 2005, 280, 3096–3103. [Google Scholar] [CrossRef] [PubMed]
- Lara-Velazquez, M.; Al-Kharboosh, R.; Jeanneret, S.; Vazquez-Ramos, C.; Mahato, D.; Tavanaiepour, D.; Rahmathulla, G.; Quinones-Hinojosa, A. Advances in Brain Tumor Surgery for Glioblastoma in Adults. Brain Sci. 2017, 7, 166. [Google Scholar] [CrossRef] [PubMed]
- Stupp, R.; Taillibert, S.; Kanner, A.; Read, W.; Steinberg, D.M.; Lhermitte, B.; Toms, S.; Idbaih, A.; Ahluwalia, M.S.; Fink, K.; et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA 2017, 318, 2306–2316. [Google Scholar] [CrossRef] [PubMed]
- Yi, G.-Z.; Huang, G.; Guo, M.; Zhang, X.; Wang, H.; Deng, S.; Li, Y.; Xiang, W.; Chen, Z.; Pan, J.; et al. Acquired temozolomide resistance in MGMT-deficient glioblastoma cells is associated with regulation of DNA repair by DHC2. Brain 2019, 142, 2352–2366. [Google Scholar] [CrossRef] [PubMed]
- Schreck, K.C.; Grossman, S.A. Role of Temozolomide in the Treatment of Cancers Involving the Central Nervous System. Oncology 2018, 32, 555–560, 569. [Google Scholar]
- Jovanović, N.; Mitrović, T.; Cvetković, V.J.; Tošić, S.; Vitorović, J.; Stamenković, S.; Nikolov, V.; Kostić, A.; Vidović, N.; Krstić, M.; et al. The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma. Medicina 2019, 55, 34. [Google Scholar] [CrossRef]
- Nava, F.; Tramacere, I.; Fittipaldo, A.; Bruzzone, M.G.; DiMeco, F.; Fariselli, L.; Finocchiaro, G.; Pollo, B.; Salmaggi, A.; Silvani, A.; et al. Survival effect of first- and second-line treatments for patients with primary glioblastoma: A cohort study from a prospective registry, 1997–2010. Neuro-Oncology 2014, 16, 719–727. [Google Scholar] [CrossRef]
- Gramatzki, D.; Roth, P.; Rushing, E.; Weller, J.; Andratschke, N.; Hofer, S.; Korol, D.; Regli, L.; Pangalu, A.; Pless, M.; et al. Bevacizumab may improve quality of life, but not overall survival in glioblastoma: An epidemiological study. Ann. Oncol. 2018, 29, 1431–1436. [Google Scholar] [CrossRef]
- Tan, A.C.; Ashley, D.M.; López, G.Y.; Malinzak, M.; Friedman, H.S.; Khasraw, M. Management of glioblastoma: State of the art and future directions. CA Cancer J. Clin. 2020, 70, 299–312. [Google Scholar] [CrossRef]
- Nguyen, H.-M.; Guz-Montgomery, K.; Lowe, D.B.; Saha, D. Pathogenetic Features and Current Management of Glioblastoma. Cancers 2021, 13, 856. [Google Scholar] [CrossRef]
- Hanschmann, E.M.; Godoy, J.R.; Berndt, C.; Hudemann, C.; Lillig, C.H. Thioredoxins, glutaredoxins, and peroxiredoxins—Molecular mechanisms and health significance: From cofactors to antioxidants to redox signaling. Antioxid. Redox Signal. 2013, 19, 1539–1605. [Google Scholar] [CrossRef]
- Chan, M.C.; Savela, J.; Ollikainen, R.K.; Teppo, H.-R.; Miinalainen, I.; Pirinen, R.; Kari, E.J.M.; Kuitunen, H.; Turpeenniemi-Hujanen, T.; Kuittinen, O.; et al. Testis-Specific Thioredoxins TXNDC2, TXNDC3, and TXNDC6 Are Expressed in Both Testicular and Systemic DLBCL and Correlate with Clinical Disease Presentation. Oxidative Med. Cell. Longev. 2021, 2021, 8026941. [Google Scholar] [CrossRef]
- Chawsheen, H.A.; Ying, Q.; Jiang, H.; Wei, Q. A critical role of the thioredoxin domain containing protein 5 (TXNDC5) in redox homeostasis and cancer development. Genes Dis. 2018, 5, 312–322. [Google Scholar] [CrossRef] [PubMed]
- Chen, D.; Zou, J.; Zhao, Z.; Tang, X.; Deng, Z.; Jia, J.; Liu, S. TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network. Cell Death Dis. 2018, 9, 1110. [Google Scholar] [CrossRef] [PubMed]
- Feng, T.; Zhao, R.; Sun, F.; Lu, Q.; Wang, X.; Hu, J.; Wang, S.; Gao, L.; Zhou, Q.; Xiong, X.; et al. TXNDC9 regulates oxidative stress-induced androgen receptor signaling to promote prostate cancer progression. Oncogene 2020, 39, 356–367. [Google Scholar] [CrossRef] [PubMed]
- Zhou, W.; Fang, C.; Zhang, L.; Wang, Q.; Li, D.; Zhu, D. Thioredoxin domain-containing protein 9 (TXNDC9) contributes to oxaliplatin resistance through regulation of autophagy-apoptosis in colorectal adenocarcinoma. Biochem. Biophys. Res. Commun. 2020, 524, 582–588. [Google Scholar] [CrossRef] [PubMed]
- Zheng, T.; Chen, K.; Zhang, X.; Feng, H.; Shi, Y.; Liu, L.; Zhang, J.; Chen, Y. Knockdown of TXNDC9 induces apoptosis and autophagy in glioma and mediates cell differentiation by p53 activation. Aging 2020, 12, 18649–18659. [Google Scholar] [CrossRef] [PubMed]
- Yuan, K.; Xie, K.; Lan, T.; Xu, L.; Chen, X.; Li, X.; Liao, M.; Li, J.; Huang, J.; Zeng, Y.; et al. TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of beta-catenin. Cell Death Differ. 2020, 27, 1355–1368. [Google Scholar] [CrossRef]
- Zhang, S.-F.; Wang, X.-Y.; Fu, Z.-Q.; Peng, Q.-H.; Zhang, J.-Y.; Ye, F.; Fu, Y.-F.; Zhou, C.-Y.; Lu, W.-G.; Cheng, X.-D.; et al. TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer. Autophagy 2015, 11, 225–238. [Google Scholar] [CrossRef]
- Timms, R.T.; Menzies, S.A.; Tchasovnikarova, I.A.; Christensen, L.C.; Williamson, J.C.; Antrobus, R.; Dougan, G.; Ellgaard, L.; Lehner, P.J. Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens. Nat. Commun. 2016, 7, 11786. [Google Scholar] [CrossRef]
- Wu, Y.; Ye, H.; Peng, B.; Jiang, H.; Tang, Q.; Liu, Y.; Xi, J.; Chen, S. MiR-643 Functions as a Potential Tumor Suppressor in Gastric Cancer by Inhibiting Cell Proliferation and Invasion via Targeting TXNDC9. Ann. Clin. Lab. Sci. 2021, 51, 494–502. [Google Scholar] [PubMed]
- Peng, P.; Cheng, F.; Dong, Y.; Chen, Z.; Zhang, X.; Guo, D.; Yu, X.; Lu, Y.; Ke, Y.; Zhang, B.; et al. High expression of TXNDC11 indicated unfavorable prognosis of glioma. Transl. Cancer Res. 2021, 10, 5040–5051. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Unternaehrer, J.J. Epithelial-mesenchymal Transition and Cancer Stem Cells: At the Crossroads of Differentiation and Dedifferentiation. Dev. Dyn. 2019, 248, 10–20. [Google Scholar] [CrossRef]
- Roche, J. The Epithelial-to-Mesenchymal Transition in Cancer. Cancers 2018, 10, 52. [Google Scholar] [CrossRef] [PubMed]
- Na, T.-Y.; Schecterson, L.; Mendonsa, A.M.; Gumbiner, B.M. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps. Proc. Natl. Acad. Sci. USA 2020, 117, 5931–5937. [Google Scholar] [CrossRef] [PubMed]
- Montalto, F.I.; De Amicis, F. Cyclin D1 in Cancer: A Molecular Connection for Cell Cycle Control, Adhesion and Invasion in Tumor and Stroma. Cells 2020, 9, 2648. [Google Scholar] [CrossRef] [PubMed]
- Fedchenko, N.; Reifenrath, J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue—A review. Diagn. Pathol. 2014, 9, 221. [Google Scholar] [CrossRef]
TXNDC11 Expression | p Value | |||
---|---|---|---|---|
Low | High | |||
Age | 1 | |||
<60 | 64 (74.4%) | 14 (16.3%) | 50 (58.1%) | |
≥60 | 22 (25.6%) | 4 (4.7%) | 18 (20.9%) | |
Gender | 1 | |||
Male | 48 (55.8%) | 10 (11.6%) | 38 (44.2%) | |
Female | 38 (44.2%) | 8 (9.3%) | 30 (34.9%) | |
WHO grade | <0.001 | |||
II | 20 (23.3%) | 12 (14.0%) | 8 (9.3%) | |
III/IV | 66 (76.7%) | 6 (7.0%) | 60 (69.8%) | |
Tumour Size | 0.789 | |||
<3 cm | 54 (62.8%) | 12 (14.0%) | 42 (48.8%) | |
≥3 cm | 32 (37.2%) | 6 (7.0%) | 26 (30.2%) | |
KPS | 0.771 | |||
<70 | 61 (70.9%) | 12 (14.0%) | 49 (57.0%) | |
≥70 | 25 (29.1%) | 6 (7.0%) | 19 (22.1%) |
Univariate | Multivariate | |||
---|---|---|---|---|
HR (95% CI) | p | HR (95% CI) | p | |
Age | 0.755 (0.419–1.360) | 0.349 | ||
Gender | 0.880 (0.534–1.451) | 0.616 | ||
WHO grade | 0.316 (0.160–0.624) | 0.01 | 0.452 (0.220–0.930) | 0.031 |
Tumour size | 1.295 (0.757–2.217) | 0.345 | ||
Radiotherapy | 1.183 (0.714–1.959) | 0.514 | ||
TMZ | 0.987 (0.599–1.626) | 0.958 | ||
KPS | 1.387 (0.798–2.408) | 0.236 | ||
TXNDC11 | 0.248 (0.117–0.524) | <0.001 | 0.334 (0.153–0.729) | 0.006 |
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Chen, Y.-T.; Chung, C.-L.; Cheng, Y.-W.; Lin, C.-J.; Tseng, T.-T.; Hsu, S.-S.; Tsai, H.-P.; Kwan, A.-L. High Thioredoxin Domain-Containing Protein 11 Expression Is Associated with Tumour Progression in Glioma. Int. J. Mol. Sci. 2023, 24, 13367. https://doi.org/10.3390/ijms241713367
Chen Y-T, Chung C-L, Cheng Y-W, Lin C-J, Tseng T-T, Hsu S-S, Tsai H-P, Kwan A-L. High Thioredoxin Domain-Containing Protein 11 Expression Is Associated with Tumour Progression in Glioma. International Journal of Molecular Sciences. 2023; 24(17):13367. https://doi.org/10.3390/ijms241713367
Chicago/Turabian StyleChen, Ying-Tso, Chia-Li Chung, Yu-Wen Cheng, Chien-Ju Lin, Tzu-Ting Tseng, Shu-Shong Hsu, Hung-Pei Tsai, and Aij-Lie Kwan. 2023. "High Thioredoxin Domain-Containing Protein 11 Expression Is Associated with Tumour Progression in Glioma" International Journal of Molecular Sciences 24, no. 17: 13367. https://doi.org/10.3390/ijms241713367