Long non-coding RNA expression profiles predict clinical phenotypes in glioma

Zhang, Xiaoqin; Sun, Stella; Pu, Jenny Kan Suen; Tsang, Anderson Chun On; Lee, Derek; Man, Venus On Ying; Lui, Wai Man; Wong, Thian‐Sze; Leung, Gilberto Ka Kit

doi:10.1016/j.nbd.2012.06.004

Cited by 331 publications

(316 citation statements)

References 79 publications

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“…Recent progress suggests that the involvement of lncRNAs in human cancers could be far more prevalent that previously appreciated. To date, lncRNA expression has not been extensively analyzed in GBM samples except in a few studies that used microarrays from TCGA and Gene Expression Omnibus (24,25). Although informative, such studies likely miss unannotated lncRNAs not represented on arrays and are often biased to polyadenylated fractions that contain fewer lncRNAs (26).…”

Section: Significancementioning

confidence: 99%

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

Pastori

Kapranov

Penas

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

186

152

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Bromodomain and extraterminal (BET) domain proteins have emerged as promising therapeutic targets in glioblastoma and many other cancers. Small molecule inhibitors of BET bromodomain proteins reduce expression of several oncogenes required for Glioblastoma Multiforme (GBM) progression. However, the mechanism through which BET protein inhibition reduces GBM growth is not completely understood. Long noncoding RNAs (lncRNAs) are important epigenetic regulators with critical roles in cancer initiation and malignant progression, but mechanistic insight into their expression and regulation by BET bromodomain inhibitors remains elusive. In this study, we used Helicos single molecule sequencing to comprehensively profile lncRNAs differentially expressed in GBM, and we identified a subset of GBM-specific lncRNAs whose expression is regulated by BET proteins. Treatment of GBM cells with the BET bromdomain inhibitor I-BET151 reduced levels of the tumorpromoting lncRNA HOX transcript antisense RNA (HOTAIR) and restored the expression of several other GBM down-regulated lncRNAs. Conversely, overexpression of HOTAIR in conjunction with I-BET151 treatment abrogates the antiproliferative activity of the BET bromodomain inhibitor. Moreover, chromatin immunoprecipitation analysis demonstrated binding of Bromodomain Containing 4 (BRD4) to the HOTAIR promoter, suggesting that BET proteins can directly regulate lncRNA expression. Our data unravel a previously unappreciated mechanism through which BET proteins control tumor growth of glioblastoma cells and suggest that modulation of lncRNA networks may, in part, mediate the antiproliferative effects of many epigenetic inhibitors currently in clinical trials for cancer and other diseases.glioblastoma | long noncoding RNAs | epigenetics | BRD4 | I-BET151

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Section: Significancementioning

confidence: 99%

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

Pastori

Kapranov

Penas

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

186

152

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“…Zhang et al32 identified 129 lncRNAs differentially expressed between glioma and normal brain tissues. Two lncRNAs, colorectal neoplasia differentially expressed (CRNDE) and HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), showed the highest expression in glioma (grade I‐IV) compared with that in normal tissue.…”

Section: Dysregulated Lncrna Expression In Glioma Pathologymentioning

confidence: 99%

“…Several studies have correlated lncRNA expression profiles with different histological subtypes and malignancy grades in gliomas 32, 36, 37. Global gene expression analyses identified 27 lncRNAs that are differentially expressed between astrocytomas and oligodendrogliomas 32.…”

Section: Dysregulated Lncrna Expression In Glioma Pathologymentioning

confidence: 99%

“…CRNDE, one of the most highly expressed lncRNAs during neuronal differentiation, in induced pluripotent stem cells (iPSCs) and within gliomas32, 35, 50 exerts its oncogenic function by promoting glioma cell growth, invasion and migration through different signalling pathways 51. Acting as a decoy, lncRNAs support glioma progression by reducing miR‐136‐5p expression, directly impacting PI3K/AKT/mTOR signalling pathways 52.…”

Section: Oncogenic Lncrnasmentioning

confidence: 99%

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Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

Pop

Enciu

Necula

et al. 2018

J Cellular Molecular Medi

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Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non‐coding RNAs (lncRNAs) and their main representatives, large intergenic non‐coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem‐like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs‐induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.

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“…These include, as examples, lncRNA signatures in neuropathological specimens from patients with AD [86], addiction to alcohol [46], addiction to heroin [45], autism [47], gliomas [87,88], Huntington's disease [89], and pituitary adenomas [90]. Importantly, these abnormal expression patterns are not only found in brain but they can also be present in more accessible fluids and tissues.…”

Section: Establishing Paradigms For Lncrna-related Pathologymentioning

confidence: 99%

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

2013

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The human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), a novel and important class of genes. Our knowledge of lncRNAs has grown exponentially since their discovery within the last decade. lncRNAs are expressed in a highly cell-and tissue-specific manner, and are particularly abundant within the nervous system. lncRNAs are subject to post-transcriptional processing and inter-and intra-cellular transport. lncRNAs act via a spectrum of molecular mechanisms leveraging their ability to engage in both sequence-specific and conformational interactions with diverse partners (DNA, RNA, and proteins). Because of their size, lncRNAs act in a modular fashion, bringing different macromolecules together within the three-dimensional context of the cell. lncRNAs thus coordinate the execution of transcriptional, post-transcriptional, and epigenetic processes and critical biological programs (growth and development, establishment of cell identity, and deployment of stress responses). Emerging data reveal that lncRNAs play vital roles in mediating the developmental complexity, cellular diversity, and activitydependent plasticity that are hallmarks of brain. Corresponding studies implicate these factors in brain aging and the pathophysiology of brain disorders, through evolving paradigms including the following: (i) genetic variation in lncRNA genes causes disease and influences susceptibility; (ii) epigenetic deregulation of lncRNAs genes is associated with disease; (iii) genomic context links lncRNA genes to disease genes and pathways; and (iv) lncRNAs are otherwise interconnected with known pathogenic mechanisms. Hence, Electronic supplementary material The online version of this article

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Long non-coding RNA expression profiles predict clinical phenotypes in glioma

Cited by 331 publications

References 79 publications

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

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