Dataset Information

Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy.

ABSTRACT: We previously observed association between variants in the plasmacytoma variant translocation 1 gene (PVT1) and end-stage renal disease (ESRD) attributed to both type 1 and type 2 diabetes, and demonstrated PVT1 expression in a variety of renal cell types. While these findings suggest a role for PVT1 in the development of ESRD, potential mechanisms for involvement remain unknown. The goal of this study was to identify possible molecular mechanisms by which PVT1 may contribute to the development and progression of diabetic kidney disease. We knocked-down PVT1 expression in mesangial cells using RNA interference, and analyzed RNA and protein levels of fibronectin 1 (FN1), collagen, type IV, alpha 1 (COL4A1), transforming growth factor beta 1 (TGFB1) and plasminogen activator inhibitor-1 (SERPINE1 or PAI-1) by qPCR and ELISA, respectively. PVT1 expression was significantly upregulated by glucose treatment in human mesangial cells, as were levels of FN1, COL4A1, TGFB1, and PAI-1. Importantly, PVT1 knockdown significantly reduced mRNA and protein levels of the major ECM proteins, FN1 and COL4A1, and two key regulators of ECM proteins, TGFB1 and PAI-1. However, we observed a higher and more rapid reduction in levels of secreted FN1, COL4A1, and PAI-1 compared with TGFB1, suggesting that at least some of the PVT1 effects on ECM proteins may be independent of this cytokine. These results indicate that PVT1 may mediate the development and progression of diabetic nephropathy through mechanisms involving ECM accumulation.

SUBMITTER: Alvarez ML

PROVIDER: S-EPMC3081298 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy.

Alvarez M Lucrecia ML DiStefano Johanna K JK

PloS one 20110422 4

We previously observed association between variants in the plasmacytoma variant translocation 1 gene (PVT1) and end-stage renal disease (ESRD) attributed to both type 1 and type 2 diabetes, and demonstrated PVT1 expression in a variety of renal cell types. While these findings suggest a role for PVT1 in the development of ESRD, potential mechanisms for involvement remain unknown. The goal of this study was to identify possible molecular mechanisms by which PVT1 may contribute to the development ...[more]

PMID: 21526116

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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

Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy.

Publications

Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy.

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