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.

Paralogous HOX13 Genes in Human Cancers

“…In addition, it is significantly correlated with VEGF expression and microvessels density, suggesting a central role of HOXB13 in HCC angiogenesis and tumor progression [116]. Finally, an altered HOXB13 expression has been described in oral cancers [117,118] and glioma patients [119].…”

“…HOXB13 appears to be under the control of a co-localizing lncRNA. HOXB13-AS1 is a 564 nucleotide- lncRNA localized on chromosome 17, adjacent to HOXB13 [120], highly expressed in several normal human tissues [121,122] and different tumor types [119,122]. HOXB13-AS1 is able to contribute to cancer cells proliferation by binding with the enhancer of zeste homolog 2 (EZH2), epigenetically suppressing HOXB13 expression of its neighbor gene [119]…”

The oncogenic role of LncRNA FAM83C-AS1 in colorectal cancer development by epigenetically inhibits SEMA3F via stabilizing EZH2

“…For example, lncRNA GHET1 indicates poor prognosis and facilitates cell proliferation through silencing KLF2 expression in hepatocellular carcinoma [ 31 ]. LncRNA HOXB13-AS1 exacerbates glioma progression by regulating HOXB13 gene methylation through interacting with EZH2 [ 22 ]. LncRNA HOTAIR motivates the self-renewal of leukemia stem cells by epigenetically silencing p15 [ 32 ].…”

“…For instance, lncRNA SLCO4A1-AS1 promotes tumor cell proliferation and metastasis via activating the β-catenin-dependent Wnt pathway in CRC [ 21 ]. LncRNA HOXB13-AS1 promotes glioma progression by regulating HOXB13 gene methylation through EZH2 [ 22 ].…”

The Nuclear Protein HOXB13 Enhances Methylmercury Toxicity by Inducing Oncostatin M and Promoting Its Binding to TNFR3 in Cultured Cells

“…HOXB13 is highly expressed in the developmental stages of mice, especially in the chorda and posterior mesoderm, and has been suggested to be involved in the formation of normal nerve tubes by the induction of apoptosis [7]. Although HOXB13 expression is probably regulated by the long noncoding RNA, HOXB13-AS, in the adult brain [8], its function in the central nervous system remains largely unknown. In contrast, HOXB13 is highly expressed in the skin and prostate as well as in some cancer cells in adults and is known to be involved in promoting carcinogenesis [9][10][11][12].…”