Abstract
BackgroundAs an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored.MethodsThe expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC.ResultsWe show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPβ, leading to the promotion of C/EBPβ transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells.ConclusionsThe present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPβ depending on its H3K27 demethylase activity.
Highlights
As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, Lysine-specific demethylase 6B (KDM6B) has been implicated in the development and malignant progression in various types of cancers
KDM6B expression was significantly increased in metastatic esophageal squamous cell carcinoma (ESCC) TCGA data set showed that there was no significant difference in KDM6B mRNA expression between esophageal cancer tissues and normal esophageal tissues, but the overall trend was upregulated (Fig. 1a)
The expression level of KDM6B was obviously increased in patients with lymph node metastasis (Fig. 1c,d). and analysis of the adjacent non-tumor esophageal tissues and ESCC tissues by IHC revealed that KDM6B expression is associated with the lymph node metastasis and the N stage of ESCC, but not with age, sex, T stage or Pathologic differentiation (Table 3)
Summary
As an H3K27me demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. Its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. Esophageal cancer (EC) is one of the most common gastrointestinal malignancies in the world. In China, esophageal squamous cell carcinoma (ESCC) is currently the major histologic subtype of esophageal cancer [2]. Despite advances in therapeutic methods, ESCC remains one of the most common malignancies in China with an overall five-year survival rate of less than 20% after surgery [3]. A better understanding of the molecular mechanisms underlying ESCC progression will supply an arm for improving the diagnosis and treatment of human ESCC. Epigenetic modification plays an important role in tumorigenesis and development
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call