Long non-coding RNAs in glioma: Functional roles and clinical perspectives

Highlights

• We discuss the aberrant lncRNA expression in glioma initiation and progression.

• We discuss the potential mechanisms underlying lncRNA dysregulation in glioma.

• We discuss the functional roles of lncRNAs in regulating glioma biological behavior.

• We discuss the potentials of lncRNAs as biomarkers and therapy targets in glioma.

Abstract

Long non-coding RNAs (lncRNAs) are a new class of non-coding gene regulators. But unlike their smaller counterparts, microRNAs, relatively less is known about the roles and functions of lncRNAs. Current evidence suggests that lncRNAs may play important roles in a wide range of biological processes in human cancers, including glioma. By acting as oncogenes or tumor suppressors, lncRNAs may contribute to glioma initiation, progression and other malignant phenotypes. Their expression profiles may also have important clinical implications in glioma subclassification and patients’ prognostication. Here, we review current evidence related to the functional roles of lncRNAs in glioma. We will discuss the aberrant lncRNA expression signatures associated with glioma initiation and progression, as well as the potential mechanisms underlying lncRNA dysregulation. We also discuss the functional roles of lncRNAs in glioma biological behavior. Finally, the potentials and prospects of employing lncRNAs as novel biomarkers and therapeutic targets for glioma clinical practice will also be addressed.

Introduction

The emerging significance of long non-coding RNAs (lncRNAs) in cancer has attracted considerable interests in recent years (Niland et al., 2012, Prensner and Chinnaiyan, 2011). While initially thought to be spurious transcriptional noise, increasing evidence began to suggest that lncRNAs indeed play critical regulatory roles in the development of many human diseases, including cancer (Gibb et al., 2011, Wapinski and Chang, 2011). Functional studies for a handful of lncRNAs revealed that the latter could regulate gene expressions at transcriptional, post-transcriptional and epigenetic levels (Mercer et al., 2009). Aberrant expressions of lncRNAs may potentially alter basic cellular biological processes and contribute to tumorigenesis (Gibb et al., 2011, Gutschner and Diederichs, 2012). Moreover, differential expressions of specific lncRNAs may correlate with disease processes, staging or other malignant phenotypes, and thus could potentially act as therapeutic targets, as well as biomarkers for diagnosis and prognosis (Qi and Du, 2013, Spizzo et al., 2012, Wahlestedt, 2013). LncRNAs are emerging as new players in cancer biology paradigm.

Gliomas account for the great majority of primary tumors in the brain (Wen and Kesari, 2008). Based on their likely cellular origins, gliomas may broadly be subclassified into astrocytomas, oligodendrogliomas, ependymomas and mixed tumors (e.g. oligoastrocytomas) (Louis et al., 2007). Within each histological subtype, they could be further categorized into grades I–IV lesions based on the degree of malignancy (Louis et al., 2007). The clinical outcomes of glioma patients depend heavily on histopathological features (Wen and Kesari, 2008). The most malignant tumor type, glioblastoma multiform (GBM, grade IV astrocytoma), is almost invariably fatal with an overall survival of just over one year only (Wen and Kesari, 2008). Despite the development of multimodal and aggressive treatments that include surgical resection, local radiotherapy and systemic chemotherapy in the past decades, patient outcomes remain unsatisfactory (Omuro and DeAngelis, 2013, Taylor, 2010). To improve treatment efficacy, a better understanding of glioma pathogenesis at the genetic and molecular levels is urgently needed (Chen et al., 2012, Jansen et al., 2010).

Recent evidence indicates that lncRNAs play important roles in glioma pathogenesis (Bian et al., 2014, Sun et al., 2013). It has been reported that lncRNAs may regulate certain tumorigenic processes in glioma such as cellular proliferation and apoptosis (Wang et al., 2012). Aberrant expressions of lncRNAs may not only reflect clinical phenotypes (Zhang et al., 2012) and patient prognosis (Zhang et al., 2013), but also can be exploited as potential therapeutic targets (Amit et al., 2012). In this review, we summarize the recent progress of lncRNA studies in glioma. We will first provide an overview on the dysregulated expressions of lncRNAs associated with glioma initiation and progression, and the potential underlying mechanisms. We will then discuss the functional roles of lncRNAs in regulating glioma biological behavior. Finally, we will discuss the potentials of lncRNAs as biomarkers for glioma diagnosis, prognostication and targeted therapy.