Serum HOTAIR and GAS5 levels as predictors of survival in patients with glioblastoma

Shen, Jie; Hodges, Tiffany R.; Song, Renduo; Gong, Yi; Calin, George A.; Heimberger, Amy B.; Zhao, Hua

doi:10.1002/mc.22739

Cited by 84 publications

(79 citation statements)

References 45 publications

(59 reference statements)

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“…Emerging evidence identifies GAS5 as a potential prognostic and diagnostic marker in hepatocellular carcinoma. 21 In this study, depression of GAS5 reduced the sensitivity of U87 cells that had high GAS5 levels to cisplatin by inhibiting cell viability, colony formation, and promoting cell apoptosis. 19 For research in glioma, GAS5 exerts an inhibitory effect on cell proliferation and malignancy of human glioma stem cell.…”

Section: Gas5 Mutes Cisplatin-activated Autophagy In a Mtor-dependementioning

confidence: 63%

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

Huo

Chen

2018

J of Cellular Biochemistry

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Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest‐specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy‐related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin‐inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5‐mediated depression in cisplatin‐evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5‐increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma.

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Section: Gas5 Mutes Cisplatin-activated Autophagy In a Mtor-dependementioning

confidence: 63%

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

Huo

Chen

2018

J of Cellular Biochemistry

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“…were associated with increased probability of OS and DFS rates in patients with GBM. 102 These results suggested that GAS5 might have great potential to be used as a therapeutic target and biomarkers for GBM. Head and neck cancer (HNC) is a heterogeneous group of cancers originating from the upper aero-digestive tract and one of the ten most frequent cancers worldwide.…”

Section: Clinical Relevancementioning

confidence: 91%

<p>Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer</p>

Yu¹,

Hann²

2019

OTT

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Long noncoding RNAs (lncRNAs) play crucial regulatory roles in fundamental biological processes, and deregulations of lncRNAs have been linked to numerous human diseases, especially cancers. Of particular interest in this regard is lncRNA GAS5, which is mainly identified as a tumor suppressor in several cancers. GAS5 was significantly low expressed in multiple cancers and was associated with clinic-pathological characteristics and patient survival, indicating a novel potential diagnostic and prognostic biomarker, and a therapeutic target for cancer. Functionally, GAS5 is involved in cell proliferation, metastasis, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and drug resistance, among others, via multiple molecular mechanisms, such as binding to DNA sequences, forming RNA-DNA triplex complex, triggering or suppressing the expression of genes, binding proteins to form chromatin-modifying complex, which activates or represses gene expression, and acting as miRNA sponge to suppress miRNA expression, leading to regulation of miRNA target genes. This review provides an overview of the current state of knowledge and role of GAS5 in clinical relevance, biological functions and molecular mechanisms underlying the dysregulation of expression and function of GAS5 in cancer. Finally, the potential prospective role as diagnostic and prognostic biomarker and therapeutic target in cancer is discussed.

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“…Higher HOTAIR levels were detected in patients' total serum and in exosomes when compared with healthy controls. 108 Shen et al 109 also reported that high levels of HOTAIR and low levels of GAS5 in serum associated with a reduced probability of 2-year survival, suggesting its potential as prognostic biomarkers.…”

Section: Circulating Tumour Nucleic Acidsmentioning

confidence: 98%

Circulating biomarkers in patients with glioblastoma

et al. 2019

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Gliomas are the most common tumours of the central nervous system and the most aggressive form is glioblastoma (GBM). Despite advances in treatment, patient survival remains low. GBM diagnosis typically relies on imaging techniques and postoperative pathological diagnosis; however, both procedures have their inherent limitations. Imaging modalities cannot differentiate tumour progression from treatment-related changes that mimic progression, known as pseudoprogression, which might lead to misinterpretation of therapy response and delay clinical interventions. In addition to imaging limitations, tissue biopsies are invasive and most of the time cannot be performed over the course of treatment to evaluate 'real-time' tumour dynamics. In an attempt to address these limitations, liquid biopsies have been proposed in the field. Blood sampling is a minimally invasive procedure for a patient to endure and could provide tumoural information to guide therapy. Tumours shed tumoural content, such as circulating tumour cells, cell-free nucleic acids, proteins and extracellular vesicles, into the circulation, and these biomarkers are reported to cross the blood-brain barrier. The use of liquid biopsies is emerging in the field of GBM. In this review, we aim to summarise the current literature on circulating biomarkers, namely circulating tumour cells, circulating tumour DNA and extracellular vesicles as potential non-invasively sampled biomarkers to manage the treatment of patients with GBM.

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Serum HOTAIR and GAS5 levels as predictors of survival in patients with glioblastoma

Cited by 84 publications

References 45 publications

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

<p>Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer</p>

Circulating biomarkers in patients with glioblastoma

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