Long non‑coding RNA PVT1 promotes glioma cell proliferation and invasion by targeting miR‑200a

Zhang, Yonghong; Ye, Gang; Luo, Yunping

doi:10.3892/etm.2018.7083

Cited by 32 publications

(31 citation statements)

References 29 publications

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“…PVT1 is a long noncoding RNA (lncRNA) that when highly expressed is associated with progression and poor prognosis in a pan-cancer cohort from TCGA. PVT1 overexpression has also been associated with poor response to chemotherapy in gliomas and squamous cell carcinoma of the head and neck 51–53 . In line with these findings, hypomethylation of the PVT1 promoter was detected in our IDH -eLB in association with overexpression of the correspondent gene in the worst prognostic subtype ( IDH wt), in both the TCGA and the current cohort samples (Fig.…”

Section: Resultsmentioning

confidence: 99%

Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers

Noushmehr

Sabedot

Malta

et al. 2019

Preprint

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24 25 26 2 SUMMARY 27Genome-wide DNA methylation profiling has shown that epigenetic abnormalities are 28 biologically important in glioma and can be used to classify these tumors into distinct prognostic 29 groups. Thus far, DNA profiling has required surgically resected glioma tissue; however, 30 gliomas release tumoral material into biofluids, such as blood and cerebrospinal fluid, providing 31 an opportunity for a minimally invasive testing. While prior studies have shown that genetic and 32 epigenetic markers can be detected in blood or cerebrospinal fluid (e.g., liquid biopsy [LB]), 33 there has been low sensitivity for tumor-specific markers. We hypothesize that the low 34 sensitivity is due to the targeted assay methods. Therefore, we profiled the genome-wide CpG 35 methylation levels in DNA of tumor tissue and cell-free DNA in serum of glioma patients, to 36 identify non-invasive epigenetic LB (eLB) markers in the serum that reflect the characteristics of 37 the tumor tissue. From the epigenetic profiles of serum from patients diagnosed with glioma 38 (N=15 IDH mutant and N=7 IDH wildtype) and with epilepsy (N=3), we defined glioma-specific 39 and IDH-specific eLB signatures (Glioma-eLB and IDH-eLB, respectively). The epigenetic 40 profiles of the matched tissue demonstrate that these eLB signatures reflected the signature of the 41 tumor. Through cross-validation we show that Glioma-eLB can accurately predict a patient's 42 glioma from those with other neoplasias (N=6 Colon; N=14 Pituitary; N=3 Breast; N=4 Lung), 43 non-neoplastic immunological conditions (N=22 sepsis; N=9 pancreatic islet transplantation), 44 and from healthy individuals (sensitivity: 98%; specificity: 99%). Finally, IDH-eLB includes 45 promoter methylated markers associated with genes known to be involved in glioma 46 tumorigenesis (PVT1 and CXCR6). The application of the non-invasive eLB signature discovered 47 109 with glioma. We showed that the eLB could differentiate glioma from non-tumoral brain tissue 110 and stratify gliomas based on prognostic class (e.g., IDH mutation status). We further observed 111 that the specificity of the eLB allowed accurate discrimination of patients with glioma from 112 patients with tumors of other origins and from patients with immune-related disease states 113 (pancreatic islet transplantation and sepsis). The IDH-eLB signature includes promoter 114 methylated markers associated with genes known to be involved in glioma tumorigenesis (e.g., 115PVT1 and CXCR6). Finally, we propose a novel clinical approach to apply the eLB panels to 116 complement the standard of care in the diagnosis and follow-up. The ability to monitor patients 117 6 by eLB has the potential to improve the pre-and post-surgical quality of care for patients 118 harboring gliomas. 119 RESULTS 120Glioma cell-free DNA methylome 121 In this study, we selected 22 matching pairs of primary glioma tissue and serum, stored at the 122 Hermelin Brain Tumor Center (HBTC) bank from patients who underwent neurosurgery at the 123 Henr...

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Section: Resultsmentioning

confidence: 99%

Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers

Noushmehr

Sabedot

Malta

et al. 2019

Preprint

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“…PVT1 modulated GREM1 and BMP downstream signaling proteins through sponging miR-128-3p, thereby promoting tumorigenesis and progression of glioma [24]. The overexpression of PVT1 in glioma tissue and cells and promotes glioma cell proliferation and invasion by targeting miR-200a [25]. PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity, migration and invasiveness [26].…”

Section: Discussionmentioning

confidence: 99%

Role of PVT1 Polymorphisms in the Glioma Susceptibility and Prognosis

Ding

Zhao

Yuan

et al. 2020

Preprint

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Background: Genetic factors play a crucial role in the glioma risk and prognosis of glioma patients. To explore the role of PVT1 polymorphism in the susceptibility and survival of glioma in the Chinese Han population, we conducted a case-control study.Methods: The three single-nucleotide polymorphisms (SNPs) in PVT1 were genotyped using Agena MassARRAY from 575 patients with glioma and 500 healthy controls. We used the χ 2 test to analyze the differences in distribution of allele and genotype between the cases and controls. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The effects of polymorphisms and clinical features on survival of glioma patients were evaluated using the log-rank test, Kaplan-Meier and Cox regression analysis.Results: We found that rs13255292 was associated with a decreased risk of glioma in the recessive model in overall or male; and rs4410871 was significantly associated with an increased the risk of glioma in age≤40 years old or female. Moreover, the extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients. However, the gender, age, tumor grade, radiotherapy and PVT1 polymorphisms have no effect on prognosis of glioma patients.Conclusions: Our results indicated that PVT1 polymorphisms (rs13255292 and rs4410871) were associated with glioma susceptibility, but have no effect on prognosis of glioma patients. Further studies with large samples are required to confirm the results.

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“…Long noncoding RNAs could mediate various cellular biological functions including cell proliferation, apoptosis, migration, and invasion in pathology evolvement 7,8 . Increasing studies revealed the implication of lncRNAs in progression of brain tumors 9,10 . To date, the molecular relationship between lncRNA and glioma onset and progression has been unveiled.…”

Section: Introductionmentioning

confidence: 99%

MYC‐activated lncRNA HNF1A‐AS1 overexpression facilitates glioma progression via cooperating with miR‐32‐5p/SOX4 axis

et al. 2020

Cancer Medicine

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Mounting literatures have revealed the crucial effects of long noncoding RNA (lncRNA) in various cancers, including glioma. HNF1A‐AS1, a novel lncRNA, is reported to modulate tumorigenesis and development of multiple cancers. However, the tumorigenic function of lncRNA HNF1A‐AS1 in glioma remains largely unknown. quantitative reverse transcription and polymerase chain reaction and western blot assays were applied to evaluate the expression of relevant mRNAs and proteins. 5‐Ethynyl‐2’‐ deoxyuridine, terminal deoxynucleotidyl transferase dUTP nick‐end labeling, flow cytometry, and transwell assays were conducted for examining the influence of HNF1A‐AS1 on glioma cell functions. The relationship among RNAs was investigated by mechanical experiments. The results demonstrated that HNF1A‐AS1 was predominantly highly expressed in glioma cell lines compared with nontumor glial epithelial cell, which was associated with the stimulation of transcription factor myelocytomatosis oncogene. Knockdown of HNF1A‐AS1 remarkably inhibited glioma cells proliferation, migration, and invasion, while accelerating cell apoptosis in vitro. Mechanically, HNF1A‐AS1 served as a miR‐32‐5p sponge. Moreover, SOX4 was discovered as a target of miR‐32‐5p. Inhibited miR‐32‐5p or upregulated SOX4 could markedly counteract the inhibitory effects of silencing HNF1A‐AS1 on glioma malignant biological behaviors. HNF1A‐AS1 exerted oncogenic property in glioma progression via upregulating miR‐32‐5p–mediated SOX4 expression, suggesting potential novel therapeutic target for future glioma treatment.

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Long non‑coding RNA PVT1 promotes glioma cell proliferation and invasion by targeting miR‑200a

Cited by 32 publications

References 29 publications

Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers

Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers

Role of PVT1 Polymorphisms in the Glioma Susceptibility and Prognosis

MYC‐activated lncRNA HNF1A‐AS1 overexpression facilitates glioma progression via cooperating with miR‐32‐5p/SOX4 axis

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