Non-coding RNA Plasmacytoma Variant Translocation Research Articles

Long noncoding RNA PVT1 regulates the proliferation and apoptosis of ARPE-19 cells in vitro via the miR-1301-3p/KLF7 axis

ABSTRACT Diabetic retinopathy (DR) as a frequent diabetic microvascular complication shows signs in one-third of diabetic patients. Long non-coding RNAs (lncRNAs) have drawn increasing attention because of their regulatory roles in DR. LncRNA plasmacytoma variant translocation 1 (PVT1) is documented to be upregulated in diabetes-related diseases, while its effects in DR remains unexplored. ARPE-19 cells under the treatment of high-glucose (HG) were used as DR cell models. The gene expression in ARPE-19 cells was examined using RT-qPCR. The viability and apoptosis of ARPE-19 cells were determined by MTT and TUNEL assays. The levels of inflammation-associated proteins or mRNA were measured using western blot. Luciferase reporter assay and RNA pull down assay were conducted for the exploration of the underlying mechanism of PVT1. PVT1 was revealed to be upregulated in DR cell models. Silencing of PVT1 promoted the viability and inhibited apoptosis of HG-stimulated ARPE-19 cells. The results revealed that PVT1 can bind with miR-1301-3p. PVT1 negatively modulated miR-1301-3p expression. Additionally, KLF7 was targeted by miR-1301-3p. PVT1 upregulated KLF7 expression by binding with miR-1301-3p. The silenced PVT1-mediated influence on cell viability and cell apoptosis was rescued by overexpression of KLF7. PVT1 suppresses proliferation and promotes apoptosis of ARPE-19 cells treated with HG in vitro by binding with miR-1301-3p to upregulate KLF7.

Long noncoding RNA PVT1 promotes chondrocyte extracellular matrix degradation by acting as a sponge for miR-140 in IL-1\u03b2-stimulated chondrocytes

BackgroundOsteoarthritis (OA) is a common degenerative joint disease, and chondrocyte extracellular matrix (ECM) degradation is one vital pathological feature of OA. Long noncoding RNA (lncRNA), a new kind of gene regulator, plays an important role in pathogenesis of many diseases like OA. Recent studies have confirmed that lncRNA plasmacytoma variant translocation 1 (PVT1) expression was upregulated in OA patients; however, its effect on ECM degradation remained unknown.MethodsCartilage tissue samples were obtained from 6 OA patients admitted in Guangdong Second Traditional Chinese Medicine Hospital. Chondrocytes were isolated and cultured from the collected cartilage tissue. Plasmid construction, RNA interference, cell transfection, fluorescence in situ hybridization (FISH), and pull-down assay were carried out during the research.ResultsIn this study, PVT1 expression was significantly increased in chondrocytes stimulated by interleukin-1β (IL-1β). In addition, inhibition of PVT1 significantly downregulated the increased expressions of ADAM metallopeptidase with thrombospondin type 1 motif-5 (ADAMTS-5) and matrix metalloproteinase-13 (MMP-13) induced by IL-1β. Further investigation revealed that PVT1 was an endogenous sponge RNA, which directly bound to miR-140 and inhibited miR-140 expression.ConclusionTo sum up, this study showed that PVT1 promoted expressions of ADAMTS-5 and MMP-13 as a competing endogenous RNA (ceRNA) of miR-140 in OA, which eventually led to aggravation of ECM degradation, thus providing a new and promising strategy for the treatment of OA.

Aberrant expression of long non-coding RNA PVT1 in allergic rhinitis children: Correlation with disease risk, symptoms, and Th1/Th2 imbalance.

BackgroundLong non‐coding RNA plasmacytoma variant translocation 1 (lnc‐PVT1) exacerbates inflammation and induces T helper (Th) 1/Th2 imbalance in allergic diseases, but its clinical role in allergic rhinitis (AR) remains unclear. Hence, we conducted this study to compare lnc‐PVT1 expression among AR children, disease controls (DCs), and health controls (HCs), aiming to investigate its clinical application in AR children.MethodsSixty AR children, 30 DCs, and 30 HCs were enrolled in the study, and then, their lnc‐PVT1 expression in peripheral blood mononuclear cell was detected. Serum interferon‐gamma (IFN‐γ), interleukin 10 (IL‐10), Th1, and Th2 cells in AR children were also analyzed. Besides, lnc‐PVT1 was also detected at Week (W)4 after treatment in AR patients.ResultsLnc‐PVT1 was upregulated in AR children compared with DCs and HCs (both p < 0.001). Lnc‐PVT1 was positively related to nasal rhinorrhea score, itching score, congestion score, and total nasal symptom score (TNSS) in AR children (all p < 0.050), instead of sneezing score (p = 0.115). Lnc‐PVT1 negatively associated with Th1 cells in AR children (p = 0.028) also exhibited a negative correlation trend with IFN‐γ (but without statistical significance) (p = 0.065). Differently, lnc‐PVT1 was positively related to Th2 cells (p = 0.012) and IL‐10 (p = 0.021) in AR children. Besides, lnc‐PVT1 and TNSS were reduced at W4 after treatment in AR children (both p < 0.001); notably, lnc‐PVT1 expression decline was correlated with TNSS decline during treatment (p = 0.013).ConclusionLnc‐PVT1 works as a biomarker, whose aberrant expression is related to disease severity, Th1/Th2 imbalance, and its decrement can reflect treatment outcome in AR children.

Evaluating the potency of blood long noncoding RNA PVT1 as candidate biomarker reflecting inflammation, multiple organ dysfunction, and mortality risk in sepsis patients.

ObjectiveLong noncoding RNA plasmacytoma variant translocation 1 (lnc‐PVT1) promotes septic inflammation and organ injuries via multiple ways, while its clinical engagement in sepsis management is indistinct. This study aimed to investigate its relationship with inflammation, multiple organ dysfunction, and mortality risk in sepsis patients.MethodsSepsis patients and age‐/gender‐matched healthy controls were enrolled; their lnc‐PVT1 expression in plasma were detected by RT‐qPCR. For sepsis patients only, the inflammatory cytokine levels (tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐17A) in plasma were detected by ELISA. According to the survival data during 28‐day follow‐up, sepsis patients were divided into sepsis survivors and sepsis deaths.ResultsLnc‐PVT1 expression was increased in sepsis patients (N = 157) compared with healthy controls (N = 80) (p < 0.001). In sepsis patients, lnc‐PVT1 was linked with higher acute physiology and chronic health evaluation II (APACHEII) score (p = 0.001), total sequential organ failure assessment (SOFA) score, and its most subitems (SOFA‐respiratory system, SOFA‐coagulation, SOFA‐liver, SOFA‐cardiovascular system, and SOFA‐renal system scores) (all p < 0.01), but not SOFA‐nervous system score (p = 0.091); it did not relate to primary infection sites either (p = 0.204). Furthermore, lnc‐PVT1 correlated with increased C‐reactive protein, TNF‐α, IL‐1β, and IL‐17 in sepsis patients (all p < 0.01). Additionally, lnc‐PVT1 expression was higher in sepsis deaths than that in sepsis survivors (p < 0.001), following receiver‐operating characteristic curve disclosed that lnc‐PVT1 predicted 28‐day septic mortality risk (area under the curve: 0.789, 95% confidence interval: 0.702–0.875).ConclusionCirculating lnc‐PVT1 exhibits the potential as a biomarker in sepsis patients to inform inflammation, multiple organ dysfunction, and mortality risk.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) modulates the proliferation and apoptosis of acute lymphoblastic leukemia cells by sponging miR-486-5p

ABSTRACT Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) is related to the progress of various cancers. Here, we illuminated the role of PVT1 in acute lymphoblastic leukemia (ALL) cell proliferation and apoptosis. PVT1 was upregulated in plasma samples from patients with ALL and ALL cell lines. PVT1 silencing repressed cell viability and enhanced cell apoptosis in Jurkat and SUP-B15 cells. PVT1 targeted microRNA-486-5p (miR-486-5p) and negatively modulated miR-486-5p expression. Upregulation of miR-486-5p decreased cell viability and increased ALL cell apoptosis. Mastermind Like Transcriptional Coactivator 3 (MAML3) was a downstream molecule of miR-486-5p and miR-486-5p mimic transfection weakened its expression in ALL cells. Rescue experiments proved that reintroduction of PVT1 counteracted the impacts of miR-486-5p in ALL cell proliferation and apoptosis. In vivo, PVT1 silencing repressed the tumor growth of SUP-B15 cells and reduced the expression of MAML3. Altogether, silencing of PVT1 inhibited ALL cell growth and induced cell apoptosis through sponging miR-486-5p.

Long non-coding RNA plasmacytoma variant translocation 1 correlates with higher inflammation, multiple organ injury and mortality risk in acute pancreatitis, especially in severe acute pancreatitis

Long non-coding RNA plasmacytoma variant translocation 1 (lnc-PVT1) possesses a good ability to regulate inflammation as well as multiple organ injury via multiple pathways, and clinically exacerbates severe acute pancreatitis (SAP) via autophagy. This study aimed to further assess the correlation of lnc-PVT1 with inflammation, multiple disease assessment scales, and prognostication in acute pancreatitis (AP) patients. Peripheral blood mononuclear cell (PBMC) samples were collected from 98 AP patients (within 24h after admission) and 50 healthy controls (HCs). lnc-PVT1 in PBMC samples was examined by reverse transcription-quantitive polymerase chain reaction. Multiple AP assessments, C-reactive protein (CRP) level, and in-hospital deaths were evaluated or recorded. lnc-PVT1 was overexpressed in AP patients compared with HCs; it was also positively correlated with Ranson's score, acute pathologic and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, and CRP level in AP patients. Besides, lnc-PVT1 disclosed a good predictive value for higher in-hospital mortality in AP patients (the area under the curve: 0.838, 95% confidence interval: 0.708-0.968). Lastly, lnc-PVT1 was generally correlated with CRP level as well as SOFA score among mild AP, moderate-severe AP, and SAP subgroups, especially in SAP subgroup; it was also correlated with higher mortality risk in SAP subgroup, but not in mild AP or moderate-severe AP subgroup. lnc-PVT1 is associated with CRP level, SOFA score, and higher mortality risk in AP patients, especially in SAP patients, indicating its potential as a biomarker for AP.

Knockdown of long non-coding RNA plasmacytoma variant translocation 1 relieves ox-LDL-induced endothelial cell injury through regulating microRNA-30c-5p in atherosclerosis

ABSTRACT Atherosclerosis (AS) is a chronic inflammatory disease involving endothelial dysfunction, and is one of the main causes of death from cardiovascular disease (CVD). Long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is overexpressed in the serum of CVD patients. However, the mechanism by which lncRNA PVT1 functions in AS remains unknown. Our research was designed to probe interactions involving lncRNA PVT1 and oxidized low-density lipoprotein (ox-LDL)-stimulated endothelial cell injury in AS. lncRNA PVT1 expression in the serum of AS patients and ox-LDL-stimulated human umbilical vein endothelial cells (HUVECs) was detected using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Cell counting kit (CCK)-8 assays, flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA) were used to determine cell proliferation, apoptosis, and levels of inflammatory cytokines, respectively. Moreover, the correlation between lncRNA PVT1 and miR-30 c-5p was predicted and verified using StarBase3.0, TargetScan, and luciferase reporter-gene assays. lncRNA PVT1 was overexpressed in the serum of AS patients and in ox-LDL-stimulated HUVECs relative to controls. Knockdown of lncRNA PVT1 facilitated proliferation, reduced apoptosis, and secretion of inflammatory factors in ox-LDL-treated HUVECs. Moreover, miR-30 c-5p was verified as a direct target of lncRNA PVT1. Furthermore, we observed that miR-30 c-5p expression was lower in AS patients than in controls. In addition, the influence of lncRNA PVT1 knockdown on ox-LDL-treated HUVECs was significantly reversed by downregulation of miR-30 c-5p. In conclusion, lncRNA PVT1 silencing inhibited HUVEC damage stimulated by ox-LDL via miR-30 c-5p regulation.

Plasmacytoma Variant Translocation-1 as Prognostic Markers in Pediatric Acute Lymphoblastic Leukemia

Introduction and Aim: Acute lymphoblastic leukemia (ALL) is the commonest form of childhood leukemia. Molecular studies can provide diagnostic and prognostic information with direct impact on the patient. Recent micro RNAs (miRNAs) studies showed that aberrant expression can be used as signatures of ALL with different subtypes and predict drug resistance. The present work aimed to evaluate the expression of Plasmacytoma Variant Translocation-1 (PVT1) in Childhood ALL patients.&#x0D; Methodology: The study included 55 children from 2 months to 15 years old; 45 patients with ALL before receiving any treatment, and 10 control children. Long non-coding RNA PVT1 expression in plasma cells was detected by reverse transcription quantitative polymerase chain reaction.&#x0D; Results: Lnc_PVT1 expression is upregulated by twelve-folds in ALL patients. At optimum cut-off value of 22.0, the biomarker has a sensitivity of 72% and 82% specificity to discriminate ALL patients from controls. Correlating the mean values of miR_1204gene fold expression with different subgroups concerning prognostic criteria, there was no statistical differences between age groups, gender, ALL phenotypes, cytogenetic abnormality, total leukocytes count, hemoglobin concentrations and platelet count. In contrast, statistical significance was detected with bone marrow blasts percentage, clinical response, and minimal residual disease.&#x0D; Conclusion: A higher expression of lnc-PVT1 was observed in ALL patients, and it had a diagnostic and prognostic potential. In addition, miR-1204 was down-regulated in pediatric ALL and associated with higher risk.

Long non-coding RNA PVT1/microRNA miR-3127-5p/NCK-associated protein 1-like axis participates in the pathogenesis of abdominal aortic aneurysm by regulating vascular smooth muscle cells

ABSTRACT The long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been implicated in the progression of abdominal aortic aneurysms (AAA). However, the detailed mechanism requires further analysis. Our study was aimed at interrogating the mechanism of PVT1 in an H2O2-induced AAA model in vitro. The expression of lncRNA PVT1, microRNA miR-3127-5p, and NCK-associated protein 1-like (NCKAP1L) was examined in AAA tissues and H2O2-treated vascular smooth muscle cells (VSMCs). Cell proliferation was assayed using Cell Counting Kit-8 (CCK8) and 5-Bromodeoxyuridine (BrdU) assays. Meanwhile, 5-Ethynyl-2′-deoxyuridine (EdU) staining was performed to assess cell apoptosis and caspase-3 activity. IL-1β and caspase-1 expression was also assessed using Western blotting to determine inflammasome activation in H2O2-treated VSMCs. Luciferase reporter assays addressed the possible interaction between miR-3127-5p and PVT1 or NCKAP1L, which was predicted by starBase analysis. PVT1 and NCKAP1L expression was elevated in AAA tissues and induced the AAA model in vitro, whereas miR-3127-5p showed the opposite trend. Functionally, PVT1 silencing promoted cell proliferation and reduced the apoptotic rate and inflammasome activation in H2O2-treated VSMCs. Mechanical investigation demonstrated that PVT1 acted as a sponge of miR-3127-5p to modulate NCKAP1L expression, resulting in suppression of VSMC proliferation, induction of apoptosis, and activation of inflammation. In conclusion, PVT1 participates in AAA progression through the miR-3127-5p/NCKAP1L axis and may be a promising biosignature and therapeutic target for AAA.

Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1

BackgroundMounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. In this study, we report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression.MethodsqRT-PCR and western blot were performed to detect the gene and protein expression. Colony formation would healing and transwell assays were used to detect cell function. Dual-luciferase reporter assay and RNA pull-down experiments were used to examine the mechanisms interaction between molecules. Orthotopic mouse models were established to evaluate the influence of PVT1 on tumor growth and metastasis in vivo.ResultsPVT1 is significant upregulated in breast cancer patients’ plasma and cell lines. PVT1 promotes breast cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, PVT1 upregulates FOXQ1 via miR-128-3p and promotes epithelial–mesenchymal transition. In addition, PVT1 binds to the UPF1 protein, thereby inducing epithelial–mesenchymal transition, proliferation and metastasis in breast cancer cells.ConclusionPVT1 may act as an oncogene in breast cancer through binding miR-128-3p and UPF1 and represents a potential target for BC therapeutic development.

Long noncoding RNA plasmacytoma variant translocation 1 promotes progression of colorectal cancer by sponging microRNA-152-3p and regulating E2F3/MAPK8 signaling.

The purpose of this study was to investigate the pathogenesis of colorectal cancer (CRC) and the effects of the long noncoding RNA plasmacytoma variant translocation 1 (PVT1) on CRC progression. Bioinformatics analysis verified PVT1 expression in tumor and normal tissues. Quantitative PCR and western blotting were used to measure mRNA and protein levels, respectively. The MTT, Transwell, colony formation, and in vivo assays were used to assess the effects of PVT1 on proliferation, migration, and invasion by CRC cells. Both PVT1 and microRNA (miR)‐152‐3p were shown to be colocalized in CRC cells using FISH assay. The target genes of miR‐152‐3p were predicted and verified by bioinformatics analysis, luciferase assay, and RNA pull‐down assay. The ChIP assay revealed that E2F3 binds with the promoter of MAPK8. We found that PVT1 was overexpressed in CRC specimens, and its expression was higher in CRC cells than normal intestinal cells. Overexpression of PVT1 enhanced the proliferation, migration, and invasion of CRC cells, whereas PVT1 knockdown inhibited these processes. MicroRNA‐152‐3p was a target of PVT1, and E2F3 was a target of miR‐152‐3p. Rescue experiments confirmed the interaction between miR‐152‐3p and PVT1 and between miR‐152‐3p and E2F3. Luciferase and ChIP assay results confirmed that E2F3 modulates the transcriptional activation of MAPK8. Long noncoding RNA PVT1 activated E2F3 signaling by sponging miR‐152‐3p. The PVT1/miR‐152‐3p/E2F3/MAPK8 axis promoted CRC progression.

Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis

ObjectivesStudies have widely explored in the filed of ischemic stroke (IS) with their focus on transcription factors. However, few studies have pivoted on sex determining region Y-box 2 (SOX2) in IS. Thus, this study is launched to figure out the mechanisms of SOX2 in IS.MethodsRat middle cerebral artery occlusion (MCAO) was established as a stroke model. MCAO rats were injected with depleted SOX2 or long non-coding RNA plasmacytoma variant translocation 1 (PVT1) to explore their roles in neurological deficits, cerebral water content, neuron survival, apoptosis and oxidative stress. The relationship among SOX2, PVT1, microRNA (miR)-24-3p and signal transducer and activator of transcription 3 (STAT3) was verified by a series of experiments.ResultsSOX2, PVT1 and STAT3 were highly expressed while miR-24-3p was poorly expressed in cerebral cortex tissues of MCAO rats. Depleted SOX2 or PVT1 alleviated brain injury in MCAO rats as reflected by neuronal apoptosis and oxidative stress restriction, brain water content reduction, and neurological deficit and neuron survival improvements. Overexpression of PVT1 functioned oppositely. Restored miR-24-3p abolished PVT1 overexpression-induced brain injury in MCAO rats. SOX2 directly promoted PVT1 expression and further increased STAT3 by sponging miR-24-3p.ConclusionThis study presents that depleting SOX2 improves IS via PVT1/miR-24-3p/STAT3 axis which may broaden our knowledge about the mechanisms of SOX2/PVT1/miR-24-3p/STAT3 axis and provide a reference of therapy for IS.

Retracted: Long Noncoding RNA Plasmacytoma Variant Translocation 1 (PVT1) Promotes Colon Cancer Progression via Endogenous Sponging miR-26b.

Retracted on authors' request due to detected data flaws. Reference: Rui Zhang, Jibin Li, Xiaofei Yan, Keer Jin, Wenya Li, Xin Liu, Jianfeng Zhao, Wen Shang, Yefu Liu. Long Noncoding RNA Plasmacytoma Variant Translocation 1 (PVT1) Promotes Colon Cancer Progression via Endogenous Sponging miR-26b. Med Sci Monit. 2018; 24: LBR8685-8692.10.12659/MSM.910955.

A positive feedback regulatory loop involving the lncRNA PVT1 and HIF-1α in pancreatic cancer.

Extreme hypoxia is among the most prominent pathogenic features of pancreatic cancer (PC). Both the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and hypoxic inducible factor-1α (HIF-1α) are highly expressed in PC patients and play a crucial role in disease progression. Reciprocal regulation involving PVT1 and HIF-1α in PC, however, is poorly understood. Here, we report that PVT1 binds to the HIF-1α promoter and activates its transcription. In addition, we found that PVT1 could bind to HIF-1α and increases HIF-1α post-translationally. Our findings suggest that the PVT1‒HIF-1α positive feedback loop is a potential therapeutic target in the treatment of PC.

Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma.

Long non-coding RNA (lncRNA) are a class of non-coding RNAs demonstrated to play pivotal roles in regulating tumor progression. Therefore, deciphering the regulatory role of lncRNA in the development of glioma may offer a promising therapeutic target for treatment of glioma. We performed RT-qPCR analysis on the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-365 in glioma tissues and cell lines. Cell proliferation and viability was assessed with CCK8 assay. Cell migration was assessed by wound healing assay. Transwell assay was used to assess cell invasion capacity. Expression of CD133+ cells was detected by flow cytometry. Western blot assay was used to detection the expression of ELF4 and stemness-related protein SOX2, Oct4 and Nanog. Bioinformatics and dual-luciferase assay were used to predict and validate the interaction between PVT1 and miR-365. Elevated PVT1 expression was observed in glioma tissues and cells. Knockdown of PVT1 and overexpression of miR-365 inhibited proliferation, migration, invasion and promoted stemness and Temozolomide (TMZ) resistance of glioma cells. PVT1 regulated ELF4 expression by competitively binds to miR-365. PVT1 regulated the stemness and sensitivity of TMZ of glioma cells through miR-365/ELF4/SOX2 axis. This study identified that PVT1 promoted glioma stemness through miR-365/ELF4/SOX2 axis.

Silencing of LncRNA-PVT1 ameliorates lipopolysaccharide-induced inflammation in THP-1-derived macrophages via inhibition of the p38 MAPK signaling pathway.

Sepsis is common in intensive care units and has a high mortality rate; yet, its pathogenesis and treatment remain unclear. Recent studies have shown that long non-coding RNA plasmacytoma variant translocation 1 (lncRNA-PVT1) plays a pro-inflammatory role in immune-related inflammatory diseases. Therefore, we investigated whether lncRNA-PVT1 plays an important pro-inflammatory effect in the inflammatory response of sepsis. Quantitative real-time PCR (RT-qPCR) was employed for the detection of lncRNA-PVT1, interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α) mRNA, and the correlations between their expressions were analyzed. After lncRNA-PVT1 knockdown by lncRNA Smart Silencer, abnormal expressions of lncRNA-PVT1, and IL-1β and TNF-α mRNA were detected. The expressions of total and phosphorylated protein of p38 were detected by western blotting. The effect of silencing lncRNA-PVT1 on p38 mitogen-activated protein kinase (MAPK) signaling pathway during lipopolysaccharide (LPS)-induced inflammation was subsequently analyzed. The MAPK selective inhibitor, SB202190, was used to block this signaling pathway, and the expressions of lncRNA-PVT1 and TNF-α were detected by RT-qPCR. Furthermore, the effect of partial blockade of the p38 MAPK signaling pathway by SB202190 on the levels of lncRNA-PVT1 was explored. Following treatment of THP-1-derived macrophages with different concentrations of LPS, the levels of lncRNA-PVT1 and IL-1β, TNF-α mRNA were increased in a dose-dependent manner. Silencing of lncRNA-PVT1 reduced the expressions of IL-1β and TNF-α mRNA via inhibition of the p38 MAPK signaling pathway. Specifically, inhibiting the p38 MAPK pathway significantly decreased the LPS-induced lncRNA-PVT1 elevation. Our observations suggest that lncRNA-PVT1 can be silenced to ameliorate LPS-induced inflammation in macrophages via inhibition of the p38 MAPK pathway. Further, the p38 MAPK pathway can regulate the expression of lncRNA-PVT1 via a positive feedback loop.

LncRNA PVT1 Facilitates Proliferation, Migration and Invasion of NSCLC Cells via miR-551b/FGFR1 Axis.

BackgroundLong non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) plays a crucial role in non-small cell lung cancer (NSCLC). Nonetheless, regulatory effects of PVT1 on functions of NSCLC cells remain blurry.MethodsRelative expression levels of PVT1, miR-551b and FGFR1 mRNA in tumor tissues and cells were examined employing quantitative real-time polymerase chain reaction (qRT-PCR); CCK-8 and BrdU assays were utilized for measuring cell viability and proliferation of H1299 and A549 cells; cell migration and invasion were detected deploying Transwell assay; dual-luciferase assay was used for the validation of binding sequence between PVT1 and miR-551b. FGFR1 expression in protein level was quantified employing Western blot.ResultsPVT1 was highly expressed in NSCLC tissues and cell lines, whereas miR-551b expression was down-regulated. Overexpression of PVT1 potentiated viability, proliferation, migration and invasion of NSCLC cells while miR-551b inhibited the biological behaviors mentioned above. MiR-551b was predicted and then confirmed as a direct downstream target of PVT1. Meanwhile, a negative correlation was observed between PVT1 expression and miR-551b expression in NSCLC tissues. Besides, PVT1 could increase FGFR1 expression by repressing miR-551b expression.ConclusionPVT1 promotes the proliferation, migration and invasion of NSCLC cells by indirectly mediating FGFR1 via targeting miR-551b.

LncRNA PVT1 promotes cetuximab resistance of head and neck squamous cell carcinoma cells by inhibiting miR-124-3p.

Cetuximab has been widely used in the clinical treatment of head and neck squamous cell carcinoma (HNSCC). However, whether long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is correlated with cetuximab resistance remains unclear. Western blot and qRT-PCR were performed to quantify the levels of genes and proteins, respectively. Cell functions were measured using Cell Counting Kit-8 (CCK-8), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry assays. The methylation level was tested using methylation-specific PCR (MSP). PVT1 was upregulated and positively correlated with the poor prognosis of HNSCC. PVT1 overexpression markedly promoted the survival and weakened the cetuximab sensitivity of HNSCC cells, while miR-124-3p overexpression showed opposite effects. Mechanistically, the silence of PVT1 indirectly promoted miR-124-3p expression by reducing its promoter methylation. Importantly, miR-124-3p overexpression impeded the regulatory roles of PVT1 overexpression. PVT1 decreased the sensitivity of HNSCC cells to cetuximab by enhancing methylation-mediated inhibition of miR-124-3p, which might provide a new insight for the cetuximab chemoresistance of HNSCC.

Long noncoding plasmacytoma variant translocation 1 facilitates the surveillance of acute respiratory distress syndrome and mortality prediction in sepsis.

Aim: We aimed to investigate the association of long noncoding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) expression with acute respiratory distress syndrome (ARDS) risk and its prognostic value for 28-day mortality in sepsis patients. Materials & methods: LncRNA PVT1 expression from 109 sepsis patients and 100 health controlswas detected. General sepsis severity was assessed using acute physiology and chronic health evaluation IIscore and sequential organ failure assessment score. Results: LncRNA PVT1 had an acceptable predictive value for higher ARDS risk, then was identified as an independent risk factor for sepsis ARDS; LncRNA PVT1 expression positively correlated with general disease severity in sepsis patients; LncRNA PVT1 was overexpressed in 28-day deaths compared with 28-day survivors in sepsis patients. Conclusion: LncRNA PVT1 may facilitate the surveillance of ARDS, general disease severity and the prediction of mortality in sepsis patients.

PVT1: A long non-coding RNA recurrently involved in neoplasia-associated fusion transcripts.

NGS technologies and bioinformatics tools allow the rapid identification of chimeric transcripts in cancer. More than 40,000 fusions are so far reported in the literature; however, for most of them, the role in oncogenesis is still not fully understood. This is the case for fusions involving the long non-coding RNA (lncRNA) Plasmacytoma variant translocation 1 (PVT1) (8q24.21). This lncRNA displays oncogenic functions in several cancer types interacting with microRNAs and proteins, but the role of PVT1 fusion transcripts is more obscure. These chimeras have been identified in both hematological malignancies and solid tumors, mainly arising from rearrangements and/or amplification of the 8q24 chromosomal region. In this review, we detail the full spectrum of PVT1 fusions in cancer, summarizing current knowledge about their genesis, function, and role as biomarkers.