ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5

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 Ge...

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Veröffentlicht in:Experimental & molecular medicine 2023, 55(0), , pp.43-54
Hauptverfasser: Jeong, Ji-Hoon, Park, Seung-Ho, Kim, Hyunhee, Nam, Hae Yun, Kim, Sung-Hak, Jeong, Minseok, Kong, Min-Jeong, Son, Jihyun, Jeong, Ji-Eun, Song, Ji-Hye, Kim, Seong Who, Choi, Kyung-Chul
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Sprache:eng
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Zusammenfassung: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. Brain tumors: Regulatory protein suppresses tumor growth The identification of a key tumor-suppressing protein could provide biomarkers and treatments for an aggressive and fast-growing form of brain and spinal cord cancer. Glioblastoma multiforme (GBM) is resistant to many forms of treatment, resulting in poor prognosis. By analyzing gene expression databases, Kyung-Chul Choi and Seong Who Kim at the University of Ulsan College of Medicine in Seoul, South Korea, and co-workers found that expression of a regulatory protein, the transcription factor ZBTB7A, is significantly reduced in patients with aggressive GBM. In experiments on mice, the researchers found that ZBTB7A inhibits expression of the EPB41L5 gene, which codes for a protein which promotes tumor growth and metastasis. Both the ZBTB7A and EPB41L5 proteins could provide useful biomarkers for GBM prognosis, and offer therapeutic targets for the
ISSN:2092-6413
1226-3613
2092-6413
DOI:10.1038/s12276-022-00908-8