Abstract
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.
Highlights
The vast majority of the human genome is transcribed, less than 3% of all transcribed genes are protein-coding
LncRNA BX111 is induced under hypoxic conditions and promotes metastasis in pancreatic cancer by activating epithelia-mesenchymal transition (EMT) via induction of ZEB1 transcription [33]
CCAT1, which is associated with cancer progression in CRC and bladder cancer, regulates apoptosis in U87 glioma cells through sponging of miR-181b [73]
Summary
The vast majority of the human genome is transcribed, less than 3% of all transcribed genes are protein-coding. Speculation over the roles of non-coding RNA (ncRNA) has ranged from junk transcripts to master epigenetic regulators. LncRNAs are versatile transcripts that play important roles in subcellular localization, transcriptional regulation, and epigenetic remodeling. As such, they can have broad phenotypic influences. With the followed by adjuvant temozolomide (TMZ) chemotherapy and radiation therapy [6]. The roles of lncRNAs in GBM have gone unstudied until very recur following [9]. The roles of lncRNAs in GBM have gone unstudied until very recently, recently, and there is evidence that these transcripts may have prognostic or even therapeutic and there is evidence that these transcripts may have prognostic or even therapeutic applications.
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