Dataset Information

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle.

ABSTRACT:

Background

The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma.

Methods

Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined.

Results

The mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma.

Conclusions

lncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients.

SUBMITTER: Austin PJ

PROVIDER: S-EPMC5338875 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle.

Austin Philip J PJ Tsitsiou Eleni E Boardman Charlotte C Jones Simon W SW Lindsay Mark A MA Adcock Ian M IM Chung Kian Fan KF Perry Mark M MM

The Journal of allergy and clinical immunology 20160702 3

<h4>Background</h4>The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma.<h4>Methods</h4>Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonse ...[more]

PMID: 27484035

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Project description:Objective: This study aimed to investigate the correlation of long noncoding RNA plasmacytoma variant translocation 1 with clinical features and prognosis in patients with multiple myeloma. Methods: The bone marrow samples were collected from 128 patients with de novo symptomatic multiple myeloma (before initial treatment) and 30 healthy donors (on the enrollment). Long noncoding RNA plasmacytoma variant translocation 1 expression in bone marrow-derived plasma cells was detected by reverse transcription quantitative polymerase chain reaction. In patients with multiple myeloma, their demographics and clinical features before treatment were collected; induction treatment response (complete response and overall response rate) and survival profiles (progression-free survival and overall survival) were assessed. Results: Expression of long noncoding RNA plasmacytoma variant translocation 1 was increased in patients with multiple myeloma compared to healthy donors. Receiver-operating characteristic curve showed that long noncoding RNA plasmacytoma variant translocation 1 distinguished patients with multiple myeloma from healthy donors with an area under the curve of 0.884 (95% confidence interval: 0.829-0.940). In patients with multiple myeloma, high expression of long noncoding RNA plasmacytoma variant translocation 1 correlated with elevated β-2 microglobulin, increased International Staging System stage, and raised Del (17p), but it did not correlate with other biochemical indexes or chromosomal abnormalities. Furthermore, long noncoding RNA plasmacytoma variant translocation 1 high expression patients presented with decreased complete response and overall response rate compared to long noncoding RNA plasmacytoma variant translocation 1 low expression patients, and high expression of long noncoding RNA plasmacytoma variant translocation 1 predicted unfavorable progression-free survival as well overall survival in patients with multiple myeloma. Conclusion: Long noncoding RNA plasmacytoma variant translocation 1 might be a potential biomarker for the supervision of disease progression and prognosis in patients with multiple myeloma.

Project description:AbstractGenetic polymorphisms of plasmacytoma variant translocation 1 can affect various tumors including gastro-intestinal, sexual hormone sensitive cancers and lymphoma. Accumulated evidence have shown that plasmacytoma variant translocation 1 acts as an oncogene and tumor suppressor in various cancers. In fact, the rs13255292 and rs2608053 single nucleotide polymorphisms of plasmacytoma variant translocation 1are known to affect lymphoma; however, their effects on gastric cancer are primarily unknown. In this study, we evaluated the association between these plasmacytoma variant translocation 1 polymorphisms and the risk of gastric cancer.In the present study, 462 patients diagnosed with gastric cancer and 377 cancer-free controls were enrolled. The TaqMan genotyping assay was used to analyze the association between rs13255292 and rs2608053 single nucleotide polymorphisms and the risk of gastric cancer.The rs2608053 dominant model (CT + TT) was associated with a decreased risk of gastric cancer in T3 + T4 (odds ratio [OR] = 0.61, confidence interval (CI) = 0.41 - 0.92, P = .019), and stage III Gastric cancer subgroups (OR = 0.59, 95% CI = 0.38 - 0.91, P = .017) compared to the CC genotype. When stratified analysis by sex was carried out, the rs13255292 dominant model (CT + TT) had a significant association with an increased risk of gastric cancer in the female negative lymph node metastasis gastric cancer subgroup, compared to the CC genotype (OR = 1.96, 95% CI = 1.16 - 3.30, P = .012). The recessive model (TT) of rs13255292 was associated with an increased risk of gastric cancer in the male T3 + T4 gastric cancer subgroups compared to the CC + CT genotype (OR = 3.82, 95% CI = 1.02 - 14.33, P = .047). The dominant model (CT + TT) of rs2608053 was related to a decreased risk of gastric cancer in male T3 + T4 (OR = 0.57, 95% CI = 0.33 - 0.98, P = .042) and stage III gastric cancer subgroups (OR = 0.49, 95% CI = 0.27 - 0.89, P = .020) compared to the CC genotype.The rs13255292 and rs2608053 single nucleotide polymorphisms in plasmacytoma variant translocation 1 may contribute to susceptibility of gastric cancer. Further studies with more subjects and different ethnic groups are needed to validate our results.

Dataset Information

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle.

Background

Methods

Results

Conclusions

Publications

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle.

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