Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Cells. 2020 Oct 28;9(11):2369. doi: 10.3390/cells9112369.
Glioblastoma (GBM) remains the most devastating primary central nervous system malignancy with a median survival of around 15 months. The past decades of research have not yielded significant advancements in the treatment of GBM. In that same time, a novel class of molecules, long non-coding RNAs (lncRNAs), has been found to play a multitude of roles in cancer and normal biology. The increased accessibility of next generation sequencing technologies and the advent of lncRNA-specific microarrays have facilitated the study of lncRNA etiology. Molecular and computational methods can be applied to predict lncRNA function. LncRNAs can serve as molecular decoys, scaffolds, super-enhancers, or repressors. These molecules can serve as phenotypic switches for GBM cells at the expression and/or epigenetic levels. LncRNAs can affect stemness/differentiation, proliferation, invasion, survival, DNA damage response, and chromatin dynamics. Aberrant expression of these transcripts may facilitate therapy resistance, leading to tumor recurrence. LncRNAs could serve as novel theragnostic or prognostic biomarkers in GBM and other cancers. RNA-based therapeutics may also be employed to target lncRNAs as a novel route of treatment for primary or recurrent GBM. In this review, we explore the roles of lncRNAs in GBM pathophysiology and posit their novel therapeutic potential for GBM.
胶质母细胞瘤（GBM）仍然是最具破坏性的原发性中枢神经系统恶性肿瘤，中位生存期约为 15 个月。过去几十年的研究在 GBM 的治疗方面并没有取得重大进展。在同一时期，一类新型分子，长链非编码 RNA（lncRNA），已被发现在癌症和正常生物学中发挥多种作用。下一代测序技术的普及和 lncRNA 特异性微阵列的出现促进了 lncRNA 病因学的研究。分子和计算方法可用于预测 lncRNA 的功能。lncRNA 可以作为分子诱饵、支架、超级增强子或抑制剂。这些分子可以作为 GBM 细胞在表达和/或表观遗传水平上的表型开关。lncRNA 可以影响干性/分化、增殖、侵袭、存活、DNA 损伤反应和染色质动力学。这些转录本的异常表达可能促进治疗耐药性，导致肿瘤复发。lncRNA 可作为 GBM 和其他癌症的新型治疗诊断或预后生物标志物。基于 RNA 的治疗方法也可用于靶向 lncRNA，作为治疗原发性或复发性 GBM 的新途径。在这篇综述中，我们探讨了 lncRNA 在 GBM 病理生理学中的作用，并提出了它们在 GBM 治疗中的新的潜在作用。
