Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian City, 116023, PR China.
Clinical Nutrition Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, PR China.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):518-524. doi: 10.1016/j.bbrc.2018.04.133. Epub 2018 Apr 21.
The mesenchymal (MES) subtype of glioblastoma (GBM) suggested worse prognosis and a more malignant phenotype in comparison with their proneural (PN) counterpart. The plasticity between PN and MES transcriptome signatures provided clinical intervention with an manner. Few LncRNA, however, have been discovered to take part in the shift between subtypes. Here, we used transcriptomic data and experimental evidences to demonstrate that silencing LncRNA LOXL1-AS1 was a new regulator of NF-κB signaling pathway through repressing RELB directly, resulting in increased marker genes of PN subtype and decreased those of MES.GBM cell proliferation was functionally suppressed by LOXL1-AS1's knockdown expression,. Furthermore, RELB's rescue could reverse LOXL1-AS1's effects partially in GBM malignant behaviors. LOXL1-AS1 could clinically serve as a poor prognostic indicator for GBM patients. In conclusion, our results suggest that LOXL1-AS1 contributes to aggressive biological processes that are related with MES phenotype via NF-κB signaling, which expand our perceptions into the underlying mechanisms in LOXL1-AS1-based and subtype transition adapted medicine for GBM management.
胶质母细胞瘤（GBM）的间质（MES）亚型与前神经元（PN）亚型相比，其预后更差，表现出更恶性的表型。PN 和 MES 转录组特征之间的可塑性为临床干预提供了一种方式。然而，很少有长链非编码 RNA（lncRNA）被发现参与亚型之间的转变。在这里，我们使用转录组数据和实验证据表明，沉默长链非编码 RNA LOXL1-AS1 通过直接抑制 RELB 成为 NF-κB 信号通路的一个新调节因子，导致 PN 亚型标志物基因的增加和 MES 标志物基因的减少。GBM 细胞的增殖通过 LOXL1-AS1 的敲低表达得到功能抑制。此外，RELB 的挽救可以部分逆转 LOXL1-AS1 在 GBM 恶性行为中的作用。LOXL1-AS1 可以作为 GBM 患者不良预后的指标。总之，我们的结果表明，LOXL1-AS1 通过 NF-κB 信号通路促进与 MES 表型相关的侵袭性生物学过程，这扩展了我们对基于 LOXL1-AS1 和亚型转换适应医学的潜在机制的认识，以用于 GBM 的管理。
