Long noncoding RNA HOXB13-AS1 regulates HOXB13 gene methylation by interacting with EZH2 in glioma.
Long noncoding RNA HOXB13-AS1 regulates HOXB13 gene methylation by interacting with EZH2 in glioma.
复制标题
长非编码RNA HOXB13-AS1通过与胶质瘤中的EZH2相互作用调节HOXB13基因甲基化
作者：
Xiong Y;Kuang W;Lu S;Guo H;Wu M;Ye M;Wu L
长链非编码RNA（lncRNA）的失调与人类疾病，特别是癌症有关。在这项研究中，我们确定了一个lncRNA，HOXB 13-AS 1，参与胶质瘤的表达。我们发现HOXB 13 ‐ AS 1在胶质瘤组织和细胞中显著上调，并与其周围基因HOXB 13水平呈负相关。体外和体内的功能实验表明，高水平的HOXB 13-AS 1通过促进细胞周期进程增加细胞增殖和肿瘤生长。相反，HOXB 13-AS 1的敲低导致细胞增殖和肿瘤生长减少。从机制上讲，我们发现HOXB 13-AS 1过表达通过使用亚硫酸氢盐测序PCR（BSP）与zeste同源物2（EZH 2）的增强子结合，增加了DNMT 3B介导的邻近基因HOXB 13启动子的甲基化，从而在表观遗传学上抑制了HOXB 13的表达。此外，使用针对EZH 2的抗体，通过RNA免疫沉淀（RIP）和染色质免疫沉淀（ChIP）试验验证了HOXB 13-AS 1和HOXB 13之间的相互作用。综上所述，我们的研究表明HOXB 13 ‐ AS 1可以通过甲基化HOXB 13启动子来调节HOXB 13基因的表达，并在胶质瘤中作为表观遗传致癌物。
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.
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