Long non-coding RNA PVT1 regulates LPS-induced acute kidney injury in an in vitro model of HK-2 cells by modulating the miR-27a-3p/OXSR1 axis.

Sepsis is a severe inflammatory disease caused by infection that can lead to multiple organ failure. Acute kidney injury (AKI) is considered to be a major cause of septic mortality in infected organs. Previous studies have revealed that non-coding RNAs are involved in AKI, but the underlying mechanisms are mostly unknown. The present study aimed to explore the role of long non-coding RNA plasmacytoma variant translocation gene 1 (lncRNA PVT1) in lipopolysaccharide (LPS)-induced acute kidney injury and the underlying mechanism. In the present study, reverse transcription-quantitative PCR analysis indicated that, in HK-2 cells treated with LPS, the mRNA expression levels of lncRNA PVT1 and oxidative stress responsive kinase 1 (OXSR1) were upregulated, and the expression of microRNA (miR)-27a-3p was downregulated. Furthermore, LPS treatment could promote the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, inhibit cell proliferation and induce apoptosis, which was rescued by PVT1 knockdown. Dual-luciferase reporter assay, RIP assay and pull-down assay results demonstrated that miR-27a-3p may be a target miR of PVT1, and that OXSR1 is the target gene of miR-27a-3p. Moreover, it was found that miR-27a-3p overexpression decreased the secretion of TNF-α and IL-6, promoted cell proliferation and inhibited apoptosis in LPS-treated HK-2 cells, which could be reversed by OXSR1 overexpression. Therefore, the present results indicated that lncRNA PVT1 regulated inflammatory cytokine secretion, cell proliferation and apoptosis by targeting miR-27a-3p, and modulating OXSR1 expression in LPS-induced HK-2 cells.

The clinical application of plasmacytoma variant translocation gene 1 in the diagnosis of rheumatoid arthritis / 中华风湿病学杂志

Objective:To explore the clinical application and diagnosis of the long non-coding RNA plasmacytoma variant translocation gene 1 (PVT1) in plasma for rheumatoid arthritis (RA).Methods:One hundred and nineteen healthy individuals were designed as healthy control (HC), 158 patients with RA, 50 patients with systemic lupus erythematosus (SLE) and 50 patients with primary Sj?gren′s syndrome (pSS) were collected from Xuzhou Central Hospital. The plasma PVT1 of HC, RA, SLE and pSS patients and were determined by real time polymerase chain reaction (qRT-PCR). The t test of two independent-samples and One-Way analysis of variance (ANOVA) were used to compare the levels of plasma PVT1 in HC, RA, SLE and pSS patients. The correlation between PVT1 and RF, IL-6 and anti-CCP of RA patients were analyzed by Spearman's rank correlation test. Receiver operating characteristic (ROC) curves were used to identify the diagnostic performance of plasma PVT1 for RA. Results:Compared to HC [(1.32±1.22)], SLE [(1.15±0.83)] and pSS patients [(1.46±0.88)], the plasma PVT1 relative expression [(3.71±2.68)] were significantly increased in RA patients ( t=8.36, P<0.01; t=6.83, P<0.01; t=5.98, P<0.01). The PVT1 had a strong positive correlation with RF, IL-6 and anti-CCP( r=0.41, P<0.01; r=0.38, P<0.01; r=0.40, P<0.01). The area under curve (AUC) of plasma of PVT1 of RA was 0.79[95% CI(0.72, 0.85); P<0.01]. At the optimal cut-off of 1.97, the diagnostic sensitivity and specificity were 68.27% and 86.45%, and in this point provided better diagnostic accuracy. When combination PVT1 with RF, the AUC was 0.88[95% CI(0.83, 0.93); P<0.01], the sensitivity and specificity were 80.22% and 82.73%. Conclusion:Plasma PVT1 has potential diagnostic value for RA, which may become a new biomarker for the diagnosis for RA patients.

The mechanism and clinical significance of long non-coding RNA plasmacytoma variant translocation gene 1 in regulating the differentiation, proliferation, invasion and metastasis of breast cancer cells through target genes / 中国医师进修杂志

Objective:To analyze the mechanism and significance of long non-coding RNA (LncRNA) plasmacytoma variant translocation gene 1 (PVT1) in regulating the proliferation, differentiation, invasion and metastasis of breast cancer cells through the target gene.Methods:From January 2018 to December 2019, the expression levels of LncRNA PVT1 and microRNA (miR)-1207-5p in breast cancer cell line MCF-7 and normal breast epithelial cell line MCF-10A were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The human breast cancer cell line MCF-7 was transfected with PVT1 overexpression vector plasmid, PVT1 silencing lentivirus plasmid and negative control plasmid, and the expression levels of PVT1 and miR-1207-5p after transfection were detected. The activities of proliferation differentiation, metastasis and invasion in transfected breast cancer cells were detected by CCK-8 method, cell scratch test and Transwell invasion experiment. The expression levels of signal transducer and activator of transcription 6 (STAT6) and P21 mRNA/protein after transfection miR-1207-5p were detected by qRT-PCR and Western blotting method.Results:The expression levels of PVT1 and miR-1207-5p in breast cancer cells were significantly higher than those in normal breast epithelial cells (1.271 ± 0.305 vs. 0.023 ± 0.006 and 1.679 ± 0.347 vs. 0.031 ± 0.009), and there were statistical differences ( P<0.01). The expression levels of PVT1 and miR-1207-5p in breast cancer cells after transfection PVT1 overexpression vector plasmid were significantly higher than those in breast cancer cells after transfection negative control plasmid and PVT1 silencing lentivirus plasmid (2.357 ± 0.271 vs. 1.000 ± 0.000 and 0.103 ± 0.021, 3.265±0.375 vs. 1.000 ± 0.000 and 0.265 ± 0.024), the indexes in breast cancer cells after transfection negative control plasmid were significantly higher than those in breast cancer cells after transfection PVT1 silencing lentivirus plasmid, and there were statistical differences ( P<0.05). The proliferation activity in breast cancer cells 48, 72, 96 and 168 h after transfected with PVT1 overexpression vector plasmid was significantly higher than that in breast cancer cells transfected with negative control plasmid and PVT1 silencing lentivirus plasmid, proliferation activity in breast cancer cells transfected with negative control plasmid was significantly higher than that in breast cancer cells transfected with PVT1 silencing lentivirus plasmid, and there were statistical differences ( P<0.05). The metastasis activity and invasion activity in breast cancer cells 24 h after transfected with PVT1 overexpression vector plasmid were significantly higher than those in breast cancer cells transfected with negative control plasmid and PVT1 silencing lentivirus plasmid, the metastasis activity in breast cancer cells transfected negative control plasmid was significantly higher than that in breast cancer cells transfected PVT1 silencing lentivirus plasmid, and there were statistical differences ( P<0.05). The STAT6 and P21 mRNA in transfection miR-1207-5p overexpression group were significantly lower than those in transfection mimic group (0.476 ± 0.102 vs. 1.000 ± 0.000 and 0.429 ± 0.097 vs. 1.132 ± 0.236), and there were statistical differences ( P<0.01); the STAT6 and P21 protein in miR-1207-5p overexpression group was significantly lower than that in mimic group (0.396 ± 0.104 vs. 1.062 ± 0.002 and 0.434 ± 0.067 vs. 1.141 ± 0.218), and there were statistical differences ( P<0.01). Conclusions:LncRNA PVT1 may be a regulated host gene of miR-1207-5p, which synergistically affects the proliferation, differentiation, invasion and metastasis of breast cancer cells through the regulation of target gene STAT6. Inhibiting the transcription of this gene may be a new research direction for breast cancer treatment.

Clinical significance of the expression of long non-coding RNA PVT1 in glioma.

BACKGROUND: Glioma is the most common primary malignant tumor in the nervous system. OBJECTIVE: To investigate the expression of long non-coding RNA Pvt1 oncogene (PVT1) in glioma and its clinical significance. METHODS: The expression levels of PVT1 were determined in 59 glioma and 10 normal tissue samples using qRT-PCR. The patients were divided into high and low expression groups and analyzed for their relationship with clinicopathological factors and the survival time using the Kaplan-Meier method. RESULTS: The expression levels of PVT1 were significantly higher in glioma tissues than in normal tissues (p< 0.01) and higher in high grade (III-IV) than in low grade (I-II) tumors (p< 0.01). Analysis showed that the PVT1 level was closely related to glioma grade (p< 0.01), but not to age, gender, Karnofsky performance status (KPS) and tumor size (p> 0.05). Receiver operator characteristic curve analysis showed an area under the curve of 0.835. Log-rank test showed that the prognosis of high PVT1 group was poorer than that of low PVT1 group (p< 0.01). CONCLUSIONS: PVT1 is highly expressed in gliomas and its level is positively related to WHO glioma grade and prognosis of gliomas. Therefore, it may be explored as a new molecular marker for predicting malignancy and prognosis of gliomas.

PVT1 regulates inflammation and cardiac function via the MAPK/NF-κB pathway in a sepsis model.

The aim of the present study was to investigate the role of plasmacytoma variant translocation gene 1 (PVT1) in the occurrence and development of sepsis-induced inflammation and cardiac dysfunction and its underlying mechanism. A sepsis rat model was first established by cecal ligation and puncture. The mRNA levels of PVT1 and microRNA-143 in the myocardial tissues of rats were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Cardiac function, levels of myocardial injury markers and inflammatory indicators were detected following PVT1 knockdown. The regulatory effect of microRNA-143 on PVT1 was assessed using a luciferase reporter gene assay and RT-qPCR analysis. The specific role of PVT1 in regulating the mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB pathway was detected using western blot analysis. PVT1 was downregulated and microRNA-143 was upregulated in the myocardial tissues of sepsis rats. The left ventricular peak pressure was markedly decreased in the sepsis rats. By contrast, the left ventricular end diastolic pressure, levels of inflammatory indicators, myocardial injury markers and complement proteins of C5 and C5a were increased in the sepsis rats. The above changes were reversed by PVT1 knockdown or the upregulation of microRNA-143. MicroRNA-143 was confirmed as being bound to PVT1 using the luciferase reporter gene assay and RT-qPCR analysis. Upregulated PVT1 was capable of activating the MAPK/NF-κB pathway. Taken together, PVT1 was upregulated in the myocardial tissues of sepsis rats, which inhibited cardiac function and promoted the secretion of inflammatory factors; and the mechanism was associated with the MAPK/NF-κB pathway.