Abstract
Glioblastoma (GBM) stem cells are resistant to cancer therapy, and therefore responsible for tumor progression and recurrence after conventional therapy. However, the molecular mechanisms driving the maintenance of stemness and dedifferentiation are poorly understood. In this study, we identified plant homeodomain finger-containing protein 20 (PHF20) as a crucial epigenetic regulator for sustaining the stem cell-like phenotype of GBM. It is highly expressed in GBM and tightly associated with high levels of aggressiveness of tumors and potential poor prognosis in GBM patients. Knockout of PHF20 inhibits GBM cell proliferation, as well as its invasiveness and stem cell-like traits. Mechanistically, PHF20 interacts with WDR5 and binds to the promoter regions of WISP1 for its expression. Subsequently, WISP1 and BGN act in concert to regulate the degradation of β-Catenin. Our findings have identified PHF20 as a key driver of GBM malignant behaviors, and provided a potential target for developing prognosis and therapy.
Highlights
Glioblastoma (GBM) is the most malignant primary tumor of the central nervous system, accounting for about 70% of intracranial primary gliomas in adults
To explore the role of plant homeodomain finger-containing protein 20 (PHF20) in GBM tumorigenesis, we firstly determined the PHF20 expression in GBM, the protein level of PHF20 in ten primary GBM cell lines was tested by western blotting: BT115, BT135, BT136, BT139, BT141, BT145, BT147, BT149, BT150, and BT156 (Supplementary Figure 1A)
We showed a marked increase of PHF20 expression in both the cytoplasm and nucleus of the glioma samples compared to the normal brain tissues (Supplementary Figure 1C)
Summary
Glioblastoma (GBM) is the most malignant primary tumor of the central nervous system, accounting for about 70% of intracranial primary gliomas in adults. Despite modern neurosurgery and intensive conventional therapy, GBM patients have limited treatment options with high rates of relapse. The average survival time of GBM patients is less than 16 months, and the overall 5year survival rate is less than 10% [1]. It is of great importance to identify key regulators that control GBM risk stratification, to aid in the development of more effective therapeutic drugs. Cancer stem cells (CSCs) have been widely recognized as a key feature of GBM [2, 3]. Recent studies show that CSCs extensively affect tumor growth, drug resistance, and recurrence and are closely related to the prognosis of patients [4,5,6].
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