KDM6B Promotes the Development, Progression and Metastasis of Oesophageal Cancer through Demethylation of Histones in the LDHA Promoter Region

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a strongly metastatic and fatal cancer. Currently, the mechanisms underlying the pathogenesis of ESCC are poorly understood. Lysine-specific demethylase 6B (KDM6B) plays a key role in the occurrence and development of various human diseases, such as cancers, immune diseases and developmental diseases. Studies have confirmed that KDM6B may exhibit both tumour-suppressive and oncogenic activities in different cancer types. However, the expression and role of KDM6B in ESCC remain unclear. Methods: KDM6B expression was analysed using The Cancer Genome Atlas (TCGA) database, and the correlation between KDM6B mRNA expression and prognosis was analysed. The expression of KDM6B in Eca109 and TE11 ESCC cells and ESCC tissues was evaluated using immunohistochemical (IHC) and Quantitative Real-time PCR (RT‒qPCR) analyses. In vitro assays were further performed to reveal the functions and characterize the upstream and downstream regulation of KDM6B expression. Results: KDM6B was overexpressed in stage T3/T4 as well as N2/N3 ESCC tissues relative to stage T1/T2 and N1/N2 ESCC tissues, respectively, and this overexpression was linked to worse prognosis of ESCC. Inhibiting KDM6B expression significantly impaired the proliferation and metastasis of ESCC cells. Lactate dehydrogenase isoform A (LDHA) plays a critical role in tumour aerobic glycolysis. The expression of LDHA was inhibited in ESCC cells to assess its role in ESCC proliferation. In this study, KDM6B knockdown suppressed not only LDHA expression but also ESCC cell proliferation. Conclusions: Based on these results, we speculate that KDM6B might be a novel therapeutic target for ESCC.