Department of Neurosurgery, Minhang Hospital, Fudan University, Minhang, Shanghai, China.
Department of Nursing, Minhang Hospital, Fudan University, Minhang, Shanghai, China.
J Cell Physiol. 2021 Jan;236(1):93-106. doi: 10.1002/jcp.29499. Epub 2020 Aug 16.
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.
胶质母细胞瘤（GBM）是成年人中最常见和最具侵袭性的脑肿瘤。越来越多的研究报告称，长非编码 RNA 在肿瘤进展过程中在转录或转录后水平上调节下游分子方面发挥着重要作用。本研究旨在探讨同源盒 B 簇反义 RNA 1（HOXB-AS1）在 GBM 中发挥作用的调节机制。我们的研究首先发现 HOXB-AS1 及其附近基因 HOXB2 和 HOXB3 在 GBM 中的表达上调，并且 HOXB-AS1 与 HOXB2 或 HOXB3 之间呈正相关。功能丧失实验和体内研究表明，沉默 HOXB-AS1、HOXB2 或 HOXB3 可抑制 GBM 的增殖并诱导其凋亡。此外，机制实验表明，HOXB-AS1 募集白细胞介素增强结合因子 3（ILF3）在转录水平上调节 HOXB2 和 HOXB3 的表达，而 HOXB-AS1 作为 miR-186-5p 的海绵体在转录后水平上调节 HOXB2 和 HOXB3 的表达。最后，通过挽救实验验证了 HOXB-AS1 在 GBM 中的调控机制。我们的结果表明，HOXB-AS1 在转录和转录后水平上促进 HOXB2 或 HOXB3 的表达。我们检测了 HOXB-AS1-ILF3-HOXB2/HOXB3 轴和 HOXB-AS1-miR-186-5p-HOXB2/HOXB3 轴驱动 GBM 进展，这可能为 GBM 患者产生更有效的诊断生物标志物和治疗靶点。
