Long noncoding RNA HOXB13-AS1 regulates HOXB13 gene methylation by interacting with EZH2 in glioma

Abstract

Dysregulation of long noncoding RNAs (lncRNAs) has been implicated in human diseases, in particular, cancers. In this study, we determined the expression of an lncRNA, HOXB13-AS1, involving in glioma. We showed that HOXB13-AS1 was significantly upregulated in glioma tissues and cells and was negatively correlated with its surrounding gene HOXB13 levels. Functional experiments in vitro and in vivo revealed that high level of HOXB13-AS1 increased cell proliferation and tumor growth by promoting cell cycle progression. Conversely, knockdown of HOXB13-AS1 resulted in decreased cell proliferation and tumor growth. Mechanistically, we showed that HOXB13-AS1 overexpression increased DNMT3B-mediated methylation of adjacent gene HOXB13 promoter by binding with the enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP), epigenetically suppressing HOXB13 expression. Additionally, the interaction between HOXB13-AS1 and HOXB13 was validated by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays using antibody against to EZH2. Taken together, our study indicated that HOXB13-AS1 could regulate HOXB13 gene expression by methylation HOXB13 promoter and acts as an epigenetic oncogenic in glioma.