ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5
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Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.
Abstract
Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.
참고문헌 (38)
- Sung, G. J., "Inhibition of TFEB oligomerization by co-treatment of melatonin with vorinostat promotes the therapeutic sensitivity in glioblastoma and glioma stem cells", J. Pineal Res, 66, pp.e12556~ (2019)
- Rodon, L., "Active CREB1 promotes a malignant TGFbeta2 autocrine loop in glioblastoma", Cancer Discov, 4, pp.1230~1241 (2014)
- Auzmendi-Iriarte, J., "Characterization of a new small-molecule inhibitor of HDAC6 in glioblastoma", Cell Death Dis, 11, pp.417~ (2020)
- Attwood, K. M., "Raloxifene prevents stress granule dissolution, impairs translational control and promotes cell death during hypoxia in glioblastoma cells", Cell Death Dis, 11, pp.989~ (2020)
- Cosset, E., "Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma", Cancer Cell, 32, pp.856~868 (2017)
- Brennan, C. W., "The somatic genomic landscape of glioblastoma", Cell, 155, pp.462~477 (2013)
- Fang, R., "EGFR", SRC, Nat. Commun, pp.2021, 12[DOI]
- Yang, F., "Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40", Nat. Commun, 12, pp.3424~ (2021)
- Choudhary, S., "Genomic analyses of early responses to radiation inglioblastoma reveal new alterations at transcription, splicing, and translation levels", Sci. Rep, 10, pp.8979~ (2020)
- Tan, M. S. Y., "A STAT3-based gene signature stratifies glioma patients for targeted therapy", Nat. Commun, 10, pp.3601~ (2019)
- Guo, M., "SFRP2 induces a mesenchymal subtype transition by suppression of SOX2 in glioblastoma", Oncogene, 40, pp.5066~5080 (2021)
- Tao, W., "Dual Role of WISP1 in maintaining glioma stem cells and tumorsupportive macrophages in glioblastoma", Nat. Commun, 11, pp.3015~ (2020)
- Ho, K. H., "miR-4286 is Involved in Connections Between IGF-1 and TGF-beta Signaling for the Mesenchymal Transition and Invasion by Glioblastomas", Cell. Mol. Neurobiol, 42, pp.791~806 (2020)
- Hasan, T., "Interleukin-8", CXCR2 signaling regulates therapy-induced plasticity and enhances tumorigenicity in glioblastoma, 2019, pp.10, 292~
- Kim, J. H., "SON drives oncogenic RNA splicing in glioblastoma by regulating PTBP1", PTBP2 switching and RBFOX2 activity, 2021, pp.12, 5551~
- Freije, W. A., "Gene expression profiling of gliomas strongly predicts survival", Cancer Res, 64, pp.6503~6510 (2004)
- Singh, A. K., "Role of ZBTB7A zinc finger in tumorigenesis and metastasis", Mol. Biol. Rep, 48, pp.4703~4719 (2021)
- Stogios, P. J., "Sequence and structural analysis of BTB domain proteins", Genome Biol, 6, pp.R82~ (2005)
- Costoya, J. A., "Functional analysis of the role of POK transcriptional repressors", Brief. Funct. Genom. Proteomic, 6, pp.8~18 (2007)
- Lee, D. K., "POZ domain transcription factor, FBI-1, represses transcription of ADH5", FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1, 2002, pp.277, 26761~26768
- Ramos Pittol, J. M., "Zbtb7a is a transducer for the control of promoter accessibility by NF-kappa B and multiple other transcription factors", PLoS Biol, 16, pp.e2004526~ (2018)
- Maeda, T., "Role of the proto-oncogene Pokemon in cellular transformation and ARF repression", Nature, 433, pp.278~285 (2005)
- Liu, X. S., "ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis", Genes Dev, 28, pp.1917~1928 (2014)
- Wang, G., "Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion", Nat. Genet, 45, pp.739~746 (2013)
- Gupta, S., "Emerging role of ZBTB7A as an oncogenic driver and transcriptional repressor", Cancer Lett, 483, pp.22~34 (2020)
- Han, D., "ZBTB7A Mediates the Transcriptional Repression Activity of the Androgen Receptor in Prostate Cancer", Cancer Res, 79, pp.5260~5271 (2019)
- Bao, S., "EPB41L5 promotes EMT through the ERK", p38 MAPK signaling pathway in esophageal squamous cell carcinoma, 2021, pp.228, 153682~
- Gosens, I., "FERM protein EPB41L5 is a novel member of the mammalian CRBMPP5polarity complex", Exp. Cell Res, 313, pp.3959~3970 (2007)
- Hirano, M., "EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelialmesenchymal transition", J. Cell Biol, 182, pp.1217~1230 (2008)
- Hashimoto, A., "ZEB1 induces EPB41L5 in the cancer mesenchymal program that drives ARF6-based invasion, metastasis and drug resistance", Oncogenesis, 5, pp.e259~ (2016)
- Wu, D., "TGF-beta1-mediated exosomal lnc-MMP2-2 increases blood-brain barrier permeability via the miRNA-1207-5p", EPB41L5 axis to promote non-small cell lung cancer brain metastasis, 2021, pp.12, 721~
- Otsuka, Y., "High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal program, correlates with poor prognosis of squamous cell carcinoma of the tongue", Cell Commun. Signal, 14, pp.28~ (2016)
- Handa, H., "Arf6 and its ZEB1-EPB41L5mesenchymal axis are required for both mesenchymal-and amoeboid-type invasion of cancer cells", Small GTPases, 9, pp.420~426 (2018)
- Jeong, M. H., "EPB41L5 Mediates TGFbeta-Induced Metastasis of Gastric Cancer", Clin. Cancer Res, 25, pp.3617~3629 (2019)
- Yee, P. P., "Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression", Nat. Commun, 11, pp.5424~ (2020)
- Maeda, T., "Regulation of hematopoietic development by ZBTB transcription factors", Int. J. Hematol, 104, pp.310~323 (2016)
- Guidez, F., "Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein", Mol. Cell. Biol, 25, pp.5552~5566 (2005)
- Yang, Y., "Pokemon(FBI-1)interacts with Smad4 to repress TGF-beta-induced transcriptional responses", Biochim. Biophys. Acta, 1849, pp.270~281 (2015)