ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5

Abstract Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, difficult to treat, and expensive. 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 GBM, but significantly reduced 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) in cancer 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-depleted U87 cells exhibited 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 inhibited GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Taken together, we discovered the role of a novel tumor suppressor, ZBTB7A, that directly inhibits GBM progression, and EPB41L5 is a therapeutic target protein for patients with GBM and an essential protein for the development of GBM therapeutics.