Researches on the Mechanism of Overexpression of Tripartite Motif Protein 48 Regulating p-ERK1/2 to Inhibit Glioma Growth

Youchuan JIANG; Yan YU; Guo ZHAO; Shicun LI; Peng DING

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Youchuan JIANG, Yan YU, Guo ZHAO, Shicun LI, Peng DING. Researches on the Mechanism of Overexpression of Tripartite Motif Protein 48 Regulating p-ERK1/2 to Inhibit Glioma Growth[J]. Journal of Kunming Medical University.

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Researches on the Mechanism of Overexpression of Tripartite Motif Protein 48 Regulating p-ERK1/2 to Inhibit Glioma Growth

Dept. of Neurosurgery，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Available Online: 2024-04-30

Abstract

Abstract

Objective To investigate the impact of TRIM48 overexpression on glioma and explore the underlying mechanism. Methods Twelve nude mice were randomly assigned into two groups: one inoculated with U87 glioma cells stably overexpressing TRIM48 （oeTRIM48 group） and the other with the control cell line （Vector group）. Tumor volume was measured every 3 days post-inoculation, and after 4 weeks, the tumors were excised and weighed. Tumor tissues underwent hematoxylin and eosin （H&E） staining, and Ki-67 expression was assessed using immunofluorescence. Additionally, the expressions of TRIM48, ERK1/2, and phosphorylated ERK1/2 （p-ERK1/2） in the tumors of nude mice and human glioma tissue arrays were analyzed through Western blot and immunohistochemistry respectively. Results Compared to the Vector group, the oeTRIM48 group exhibited significantly reduced tumor volume and weight （P < 0.0001）. H&E staining indicated a decrease in nuclei and mitotic count in the oeTRIM48 group. Furthermore, Ki-67 expression was significantly lower in the oeTRIM48 group than that in the Vector group （P < 0.0001）. The oeTRIM48 group also showed a significantly lower expression of p-ERK1/2 protein compared to the Vector group （P < 0.01）. Immunohistochemistry on tissue microarrays revealed the high expression of TRIM48 and low expression of p-ERK1/2 in adjacent non-tumoral tissues, with the opposite pattern observed in tumor tissues. Conclusion Overexpression of TRIM48 inhibits the growth and proliferation of glioma, potentially through modulation of the ERK1/2 signaling pathway.
- TRIM48,
- Glioma,
- ERK1/2

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References(29)

References

[1]	Omuro A,DeAngelis L M. Glioblastoma and other malignant gliomas: A clinical review[J]. Jama,2013,310(17):1842-1850. doi: 10.1001/jama.2013.280319
[2]	国家卫生健康委员会医政医管局,中国抗癌协会脑胶质瘤专业委员会,中国医师协会脑胶质瘤专业委员会. 脑胶质瘤诊疗指南(2022版)[J]. 中华神经外科杂志,2022,38(8):757-777. doi: 10.3760/cma.j.cn112050-20220510-00239
[3]	Ostrom Q T,Bauchet L,Davis F G,et al. The epidemiology of glioma in adults: A "state of the science" review[J]. Neuro Oncol,2014,16(7):896-913. doi: 10.1093/neuonc/nou087
[4]	Schaff L R,Mellinghoff I K. Glioblastoma and other primary brain malignancies in adults: A review[J]. Jama,2023,329(7):574-587.
[5]	Ozato K,Shin D M,Chang T H,et al. TRIM family proteins and their emerging roles in innate immunity[J]. Nat Rev Immunol,2008,8(11):849-860. doi: 10.1038/nri2413
[6]	Hatakeyama S. TRIM proteins and cancer[J]. Nat Rev Cancer,2011,11(11):792-804. doi: 10.1038/nrc3139
[7]	Watanabe M,Hatakeyama S. TRIM proteins and diseases[J]. J Biochem,2017,161(2):135-144.
[8]	Menon S,Goldfarb D,Ho C T,et al. The TRIM9/TRIM67 neuronal interactome reveals novel activators of morphogenesis[J]. Mol Biol Cell,2021,32(4):314-330. doi: 10.1091/mbc.E20-10-0622
[9]	Montell D J. TRIMing neural connections with ubiquitin[J]. Dev Cell,2019,48(1):5-6. doi: 10.1016/j.devcel.2018.12.012
[10]	Magiera M M,Mora S,Mojsa B,et al. Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in neurons[J]. Cell Death Differ,2013,20(2):281-292. doi: 10.1038/cdd.2012.124
[11]	Venuto S,Castellana S,Monti M,et al. TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways[J]. Biochim Biophys Acta Gen Subj,2019,1863(2):491-501. doi: 10.1016/j.bbagen.2018.12.001
[12]	Zhang C,Mukherjee S,Tucker-Burden C,et al. TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3[J]. Mol Oncol,2017,11(3):280-294. doi: 10.1002/1878-0261.12034
[13]	Deng Y,Zhu H,Xiao L,et al. Circ_0005198 enhances temozolomide resistance of glioma cells through miR-198/TRIM14 axis[J]. Aging (Albany NY),2020,13(2):2198-2211.
[14]	Meng L,Wang Y,Tu Q,et al. Circular RNA circ_0000741/miR-379-5p/TRIM14 signaling axis promotes HDAC inhibitor (SAHA) tolerance in glioblastoma[J]. Metab Brain Dis,2023,38(4):1351-1364.
[15]	Zhang L H,Yin Y H,Chen H Z,et al. TRIM24 promotes stemness and invasiveness of glioblastoma cells via activating Sox2 expression[J]. Neuro Oncol,2020,22(12):1797-1808. doi: 10.1093/neuonc/noaa138
[16]	Han K,Lou D I,Sawyer S L. Identification of a genomic reservoir for new TRIM genes in primate genomes[J]. PLoS Genet,2011,7(12):e1002388. doi: 10.1371/journal.pgen.1002388
[17]	Xue L P,Lu B,Gao B B,et al. Overexpression of tripartite motif-containing 48 (TRIM48) inhibits growth of human glioblastoma cells by suppressing extracellular signal regulated kinase 1/2 (ERK1/2) pathway[J]. Med Sci Monit,2019,25(1):8422-8429.
[18]	Jin Q,Zhang W,Qiu X G,et al. Gene expression profiling reveals Ki-67 associated proliferation signature in human glioblastoma[J]. Chin Med J (Engl),2011,124(17):2584-2588.
[19]	Yang P,Wang Y,Peng X,et al. Management and survival rates in patients with glioma in China (2004-2010): A retrospective study from a single-institution[J]. J Neurooncol,2013,113(2):259-266. doi: 10.1007/s11060-013-1103-9
[20]	Sun X,Kaufman P D. Ki-67: More than a proliferation marker[J]. Chromosoma,2018,127(2):175-186. doi: 10.1007/s00412-018-0659-8
[21]	Cuylen S,Blaukopf C,Politi A Z,et al. Ki-67 acts as a biological surfactant to disperse mitotic chromosomes[J]. Nature,2016,535(7611):308-312. doi: 10.1038/nature18610
[22]	Mrouj K,Andr é s-S á nchez N,Dubra G,et al. Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis[J]. Proc Natl Acad Sci U S A,2021,118(10):e2026507118. doi: 10.1073/pnas.2026507118
[23]	Theresia E,Malueka R G,Pranacipta S,et al. Association between Ki-67 labeling index and histopathological grading of glioma in indonesian population[J]. Asian Pac J Cancer Prev,2020,21(4):1063-1068. doi: 10.31557/APJCP.2020.21.4.1063
[24]	Yu Z,Ye S,Hu G,et al. The RAF-MEK-ERK pathway: Targeting ERK to overcome obstacles to effective cancer therapy[J]. Future Med Chem,2015,7(3):269-289. doi: 10.4155/fmc.14.143
[25]	Bhattacharya D,Chaudhuri S,Singh M K,et al. T11TS inhibits angiopoietin-1/Tie-2 signaling,EGFR activation and Raf/MEK/ERK pathway in brain endothelial cells restraining angiogenesis in glioma model[J]. Exp Mol Pathol,2015,98(3):455-466. doi: 10.1016/j.yexmp.2015.03.026
[26]	Cheng M,Liu L. MUC15 promotes growth and invasion of glioma cells by activating Raf/MEK/ERK pathway[J]. Clin Exp Pharmacol Physiol,2020,47(6):1041-1048. doi: 10.1111/1440-1681.13277
[27]	Li Q,Zhang L,Yang Q,et al. Thymidine kinase 1 drives hepatocellular carcinoma in enzyme-dependent and -independent manners[J]. Cell Metab,2023,35(6):912-927. doi: 10.1016/j.cmet.2023.03.017
[28]	Hirata Y. Reactive oxygen species (ROS) signaling: Regulatory mechanisms and pathophysiological roles][J]. Yakugaku Zasshi,2019,139(10):1235-1241. doi: 10.1248/yakushi.19-00141
[29]	Hirata Y,Katagiri K,Nagaoka K,et al. TRIM48 promotes ASK1 activation and cell death through ubiquitination-dependent degradation of the ASK1-negative regulator PRMT1[J]. Cell Rep,2017,21(9):2447-2457. doi: 10.1016/j.celrep.2017.11.007

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