Low expression of endothelin receptor B (EDNRB) is related to H3K9me3 binding with the EDNRB promoter region and is associated with the clinical T tumor stage in salivary adenoid cystic carcinoma

Abstract

Objective: To investigate the endothelin receptor B (EDNRB) expression in salivary adenoid cystic carcinoma (ACC) and the mechanism of the regulation of EDNRB expression.

Study design: After screening, EDNRB was selected, and the expression was detected using immunohistochemistry in 33 ACC samples (including 6 clinical tumor stage 1 [T1] patients, 13 T2 patients, 9 T3 patients, and 5 T4 patients) and 20 adjacent glands. Interaction between the EDNRB promoter region and histone H3 lysine 9 trimethylation (H3K9me3) was examined using chromatin immunoprecipitation (ChIP) in combination with ChIP-polymerase chain reaction (ChIP-PCR). EDNRB expression in ACC cells treated with chaetocin was detected using quantitative real-time PCR (qRT-PCR) and Western blot tests.

Results: EDNRB expression was lower in ACC than that in adjacent glands (P = .006). The expression of EDNRB in patients with advanced T stage was lower than that in patients with early T stage (P = .024). The low EDNRB gene expression group had more H3K9me3 binding regions in the gene promoter (P = .003). EDNRB gene expression significantly increased in the ACC cell lines after treatment with chaetocin. Chaetocin could reduce the interaction between the EDNRB promoter and H3K9me3.

Conclusions: H3K9me3 binding to the EDNRB promoter region could reduce the EDNRB expression. Low EDNRB expression played a role in the progression of ACC tumors.