Abstract
Gliomas are the most common and malignant primary brain tumors. Various hallmarks of glioma, including sustained proliferation, migration, invasion, heterogeneity, radio- and chemo-resistance, contribute to the dismal prognosis of patients with high-grade glioma. Dysregulation of cancer driver genes is a leading cause for these glioma hallmarks. In recent years, a new mechanism of post-transcriptional gene regulation was proposed, i.e., “competing endogenous RNA (ceRNA).” Long non-coding RNAs, circular RNAs, and transcribed pseudogenes act as ceRNAs to regulate the expression of related genes by sponging the shared microRNAs. Moreover, coding RNA can also exert a regulatory role, independent of its protein coding function, through the ceRNA mechanism. In the latest glioma research, various studies have reported that dysregulation of certain ceRNA regulatory networks (ceRNETs) accounts for the abnormal expression of cancer driver genes and the establishment of glioma hallmarks. These achievements open up new avenues to better understand the hidden aspects of gliomas and provide new biomarkers and potential efficient targets for glioma treatment. In this review, we summarize the existing knowledge about the concept and logic of ceRNET and highlight the emerging roles of some recently found ceRNETs in glioma progression.
Highlights
Gliomas are the most common and malignant primary brain tumors, accounting for about 30% of all primary brain tumors and 80% of malignant ones (Weller et al, 2015)
MiRNAs miRNAs are small single-stranded RNAs that play key roles in competing endogenous RNA (ceRNA) crosstalk. They bind to miRNA response elements (MREs) on target RNAs through sequence complementarity, which reduces the stability of targets or restricts their translation
Each miRNA can regulate up to thousands of target RNAs, and miRNAs can act in a combinatorial manner if a target RNA has multiple different MREs. miRNA-mediated regulation is estimated to affect a large proportion of human transcriptome, which makes miRNA an important modulator in numerous diseases, including various types of cancers
Summary
Gliomas are the most common and malignant primary brain tumors, accounting for about 30% of all primary brain tumors and 80% of malignant ones (Weller et al, 2015). Research over the past decade using advanced sequencing technologies has unraveled molecular alterations or biomarkers underlying gliomas, which updated our understanding of glioma’s biology and resulted in a new classification system (Louis et al, 2016) with more precision for gliomas. This system integrated histology and molecular biomarkers, including IDH (encoding isocitrate dehydrogenase) mutation and 1p/19q-codeletion status (Louis et al, 2016).
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