HOXB-AS1 accelerates the tumorigenesis of glioblastoma via modulation of HOBX2 and HOBX3 at transcriptional and posttranscriptional levels
HOXB-AS1 accelerates the tumorigenesis of glioblastoma via modulation of HOBX2 and HOBX3 at transcriptional and posttranscriptional levels
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DOI：
10.1002/jcp.29499
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发表时间：
2020-08-16
影响因子：
5.6
通讯作者：
Xu, Fulin
中科院分区：
文献类型：
--
作者：
Bi, Yongyan;Mao, Yuhang;Xu, Fulin
胶质母细胞瘤（GBM）是成人中最普遍、最具侵袭性的脑肿瘤。越来越多的研究报道，长链非编码rna在肿瘤进展的转录或转录后水平调控下游分子中起着至关重要的作用。本研究旨在探讨homobox B cluster反义RNA 1 （HOXB-AS1）在GBM中的调控机制。本研究首次发现HOXB-AS1及其附近基因HOXB2和HOXB3在GBM中表达上调，并与HOXB2或HOXB3呈正相关。功能缺失实验和体内研究发现，沉默HOXB-AS1、HOXB2或HOXB3抑制了GBM的增殖并诱导了细胞凋亡。此外，机制实验表明，HOXB-AS1募集白细胞介素增强子结合因子3 （interleukin enher -binding factor 3, ILF3）在转录水平调控HOXB2和HOXB3的表达，HOXB-AS1海吸miR-186-5p在转录后水平调控HOXB2和HOXB3表达。最后，通过救援实验验证HOXB-AS1在GBM中的调控机制。我们的研究结果表明，HOXB-AS1在转录和转录后水平上促进HOXB2或HOXB3的表达。我们检测到驱动GBM进展的HOXB-AS1-ILF3-HOXB2/HOXB3轴和HOXB-AS1-miR-186-5p-HOXB2/HOXB3轴，这可能会为GBM患者产生更有效的诊断生物标志物和治疗靶点。
Glioblastoma (GBM) is the most universal and invasive brain tumor among adults. Increasing studies have reported that long noncoding RNAs play vital roles in regulating downstream molecules at the transcriptional or posttranscriptional level in tumor progression. The purpose of the current research was to inquire the modulation mechanism by which homeobox B cluster antisense RNA 1 (HOXB-AS1) functioned in GBM. Our study first discovered the lifted expression of HOXB-AS1 and its nearby genes HOXB2 and HOXB3 in GBM and the positive relationship between HOXB-AS1 and HOXB2 or HOXB3. Loss-of-function assays and in vivo study detected that silencing of HOXB-AS1, HOXB2, or HOXB3 restrained the proliferation and induced the apoptosis in GBM. In addition, mechanism experiments demonstrated that HOXB-AS1 recruited interleukin enhancer-binding factor 3 (ILF3) to regulate HOXB2 and HOXB3 expression at the transcriptional level, and HOXB-AS1 sponged miR-186-5p to modulate HOXB2 and HOXB3 expression at posttranscriptional level. Finally, the regulatory mechanism of HOXB-AS1 in GBM was certified through rescue experiments. Our results indicated that HOXB-AS1 boost the HOXB2 or HOXB3 expression at the transcriptional and posttranscriptional levels. We detected the HOXB-AS1-ILF3-HOXB2/HOXB3 axis and HOXB-AS1-miR-186-5p-HOXB2/HOXB3 axis driving the GBM progression, which might generate more effective diagnostic biomarkers and therapeutic targets for patients with GBM.