Uncovering the roles of long noncoding RNAs in neural development and glioma progression

Abstract

In the past decade, thousands of long noncoding RNAs (lncRNAs) have been identified, and emerging data indicate that lncRNAs can have important biological functions and roles in human diseases including cancer. Many lncRNAs appear to be expressed specifically in the brain, and the roles of lncRNAs in neural stem cells (NSCs) and brain development are now beginning to be discovered. Here we review recent advances in understanding the diversity of lncRNA structure and functions in NSCs and brain development. NSCs in the adult mouse ventricular-subventricular zone (V-SVZ) generate new neurons throughout life, and we discuss how key elements of this adult neurogenic system have facilitated the discovery and functional characterization of known and novel lncRNAs. A review of lncRNAs described in other NSC systems reveals a variety of molecular mechanisms, including binding and recruitment of transcription factors, epigenetic modifiers, and RNA-splicing factors. Finally, we review emerging evidence indicating that specific lncRNAs can be key players driving glial malignancies, and discuss next steps towards an in vivo understanding of lncRNA function in development and disease.

Long noncoding RNA BDNF-AS regulates ketamine-induced neurotoxicity in neural stem cell derived neurons

“…Emerging evidence has demonstrated that, families of long noncoding RNAs (lncRNAs) played important roles in regulating various biological or pathological processes in both human and animals [1][2][3]. In cancers, lncRNAs were demonstrated to be critical regulators in carcinogenesis, tumor maturation, metastasis or apoptosis [1,4,5].…”

“…In cancers, lncRNAs were demonstrated to be critical regulators in carcinogenesis, tumor maturation, metastasis or apoptosis [1,4,5]. LncRNAs were also shown to be actively involved in many aspects of neuronal development or neural diseases, such as neurogenesis, neural degeneration or regeneration in both central and peripheral nerve systems [2,3,6,7].…”

Mouse models of Down syndrome: gene content and consequences

“…Some lncRNAs have been shown to regulate transcription of genes either neighboring their site of synthesis or at distal locations through interactions with chromatin (Vance and Ponting 2014). In stem cell biology, lncRNAs have been shown to regulate genes involved in neurogenesis, epidermal differentiation, and myoblast progenitors (Ng et al 2013; Ramos et al 2015; Lopez-Pajares et al 2015; Ballarino et al 2015), and to participate directly in regulation of the pluripotent state in embryonal stem cells (Flynn and Chang 2014). Some lncRNAs function as tumor suppressors, others as oncogenes, and some alter the stability of mRNAs or the efficiency of translation (Zhou et al 2012; Gupta et al 2010; Mercer et al 2009).…”

Integrating RNA sequencing into neuro-oncology practice

“…(103, 104) The lncRNAs HOTAIR and Pnky have been proposed as therapeutic targets in glioma based on their overexpression in tumor cells and role in inhibiting differentiation. (105, 106)…”