STAT3 is a key molecule in the oncogenic behavior of diffuse intrinsic pontine glioma

作者：Jinju Park, Woochan Lee, Sangil Yun, Saet Pyoul Kim, Kyung Hyun Kim, Jong‐Il Kim, Seung‐Ki Kim, Kyu‐Chang Wang, Ji Yeoun Lee · 发表于：Oncology Letters · 年份：2020 · DOI：10.3892/ol.2020.11699 · 被引用次数：15 · 研究领域：Cytokine Signaling Pathways and Interactions、MicroRNA in disease regulation、Circular RNAs in diseases

Diffuse intrinsic pontine glioma (DIPG) is one of the most lethal childhood brain tumors. This tumor is unique because it is detected exclusively in the ventral pons of patients aged between 6 and 7 years, which suggests a developmental nature of its formation. Signal transducer and activator of transcription 3 (STAT3) is a critical molecule for the differentiation of neural stem cells into astrocytes during neurodevelopment. Additionally, STAT3 is associated with oncogenesis and the epithelial-mesenchymal transition (EMT) in various types of tumor. In recent years, several studies have demonstrated the oncogenic role of STAT3 in high-grade gliomas. However, the role of STAT3 in DIPG at the cellular level remains unknown. To assess the possible association between gliogenesis and DIPG, the expression levels of various molecules participating in the differentiation of neural stem cells were compared between normal brain control tissues and DIPG tissues using open public data. All of the screened genes exhibited significantly increased expression in DIPG tissues compared with normal tissues. As STAT3 expression was the most increased, the effect of STAT3 inhibition in a DIPG cell line was assessed via STAT3 short hairpin (sh)RNA transfection and treatment with AG490, a STAT3 inhibitor. Changes in viability, apoptosis, EMT and radiation therapy efficiency were also evaluated. Downregulation of STAT3 resulted in decreased cyclin D1 expression and cell viability, migration and inv...