lncRNA Plasmacytoma Variant Translocation 1 Research Articles

LncRNAPVT1 is Associated with Cancer-Associated Fibroblasts Proliferation Through Regulating TGF-βin Oral Squamous Cell Carcinoma

ABSTRACT Introduction Human oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and has a poor survival rate. Cell-cell communication between OSCC cells and cancer-associated fibroblasts (CAFs) plays important roles in OSCC progression. We previously demonstrated that CAFs promote OSCC cell migration and invasion. However, how OSCC cells influence CAFs proliferation is unknown. Methods Knockdown of PVT1 was confirmed using lentivirus infection technique. CAFs in tissues were identified by staining the cells with α-SMA using immunohistochemical technique. CCK-8 assay was used to evaluate cell proliferation. The mRNA level of a gene was measured by qRT-PCR. Secreted TGF-β were detected using ELISA assay. Results We found that knockdown of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was associated with a low density of CAFs in xenograft tumors in mice; further analysis revealed that PVT1 in OSCC cells induced CAF proliferation through transforming growth factor (TGF)-β. Discussion Our results demonstrate that lncRNA PVT1 in tumor cells participates in CAF development in OSCC by regulating TGF-β. This study revealed a new mechanism by which PVT1 regulates OSCC progression and PVT1 is a potential therapeutic target in OSCC

LncRNA PVT1 facilitates the growth and metastasis of colorectal cancer by sponging with miR-3619-5p to regulate TRIM29 expression.

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis. Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo. PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells. We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.

LncRNA PVT1 induces apoptosis and inflammatory response of bronchial epithelial cells by regulating miR-30b-5p/BCL2L11 axis in COPD

BackgroundChronic obstructive pulmonary disease (COPD) is a serious health burden worldwide with high mortality. LncRNA plasmacytoma variant translocation 1 (PVT1) has been illustrated to serve as a biomarker for COPD progression. Nonetheless, its specific functions and mechanisms in COPD are unclarified.MethodsCigarette smoke extract (CSE) was utilized to stimulate 16HBE cells, and cigarette smoke combining with lipopolysaccharide (LPS) was employed to induce COPD in rats. Western blotting and RT-qPCR were utilized for measuring protein and RNA levels. Flow cytometry was implemented for detecting cell apoptosis. Concentrations of inflammatory factors TNF-α and IFN-γ were examined using ELISA. Luciferase reporter assay was utilized for verifying the interaction between molecules. Hematoxylin–eosin staining was performed for histological analysis of rat lung tissues.ResultsPVT1 was highly expressed in CSE-stimulated 16HBE cells and the lungs of COPD rats. PVT1 depletion restored the viability, restrained apoptosis and hindered inflammatory cytokine production in 16HBE cells under CSE treatment and alleviated pathological damages in COPD rats. PVT1 bound to miR-30b-5p and miR-30b-5p targeted BCL2 like 11 (BCL2L11). Overexpressing BCL2L11 offset the above effects mediated by PVT1 in CSE-triggered 16HBE cells.ConclusionPVT1 enhances apoptosis and inflammation of 16HBE cells under CSE stimulation by modulating miR-30b-5p/BCL2L11 axis.

Long Non-Coding RNA Plasmacytomavariant Translocation1 as ceRNA Adsorbs miR-195 to Relieve Osteoarthritis Symptoms

This study aimed to investigate the role of the long non-coding RNA plasmacytomavariant translocation1 (LncRNA PVT1) in the development of osteoarthritis (OA). The study used mice and performed DMM surgery to establish an OA model. PVT1 and miR-195 agomir were inhibited in the knee joints, and cartilage tissue specimens were collected for gene expression analysis, apoptotic protein detection, histopathological observation, and Mankin’s score evaluation. Enzymelinked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in peripheral blood and cartilage tissues. Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining was used to detect cartilage cell apoptosis. The results indicated that the OA group had higher plasmacytomavariant translocation1 (PVT1) expression and lower miR-195 expression than the sham-operated group. PVT1 was found to act as a molecular sponge for miR-195 through a dual-luciferase reporter assay. Knocking down PVT1 or upregulating miR-195 significantly attenuated inflammation and apoptosis in the bone joints of OA mice. This study provides new insights into the mechanism of OA progression and suggests that regulating the PVT1-miR-195 axis may be beneficial for improving the inflammatory microenvironment of cartilage tissue and apoptosis.

LncRNA PVT-1 promotes osteosarcoma cancer stem-like properties through direct interaction with TRIM28 and TSC2 ubiquitination.

Osteosarcoma, the most common pediatric bone tumor, is an aggressive heterogeneous malignancy defined by complex chromosomal aberrations. Overall survival rates remain at ~70%, but patients with chemoresistant or metastatic disease have extremely poor outcomes of <30%. A subgroup of tumors harbor amplification of chromosome 8q24.2 and increased expression of the oncogenic long noncoding RNA (lncRNA) Plasmacytoma Variant Translocation-1 (PVT-1), which is associated with an extremely poor clinical prognosis. This study demonstrates that PVT-1 is critical for osteosarcoma tumor-initiation potential. Chromatin Hybridization by RNA Purification analysis identified Tripartite-Motif Containing Family 28 (TRIM28) as a novel PVT-1 binding partner. Mechanistically, co-immunoprecipitation studies showed the PVT-1/TRIM28 complex binds and increases SUMOylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (Vps34), which leads to enhanced ubiquitination and degradation of tumor suppressor complex 2 (TSC2), thus contributing to increased self-renewal and stem cell phenotypes. Furthermore, we identified that osteosarcoma cells with increased PVT-1 have enhanced sensitivity to the SUMOylation inhibitor, TAK-981. Altogether, this study elucidated a role for PVT-1 in the enhancement of cancer stem-like behaviors, including migration and invasion, in osteosarcoma, and identified the novel PVT-1/TRIM28 axis signaling cascade as a potential therapeutic target for osteosarcoma treatment.

LncRNA PVT1 is a novel mediator promoting the angiogenesis response associated with collateral artery formation.

Angiogenesis plays a key role in coronary collateral circulation (CCC), the compensatory formation of new blood vessels during chronic total coronary occlusion. This study aimed to determine whether plasmacytoma variant translocation 1 (PVT1), a long non-coding (lnc) RNA involved in tumor angiogenesis, plays a role in regulating angiogenesis during chronic coronary ischemia. Patients with coronary artery disease, and ≥90% stenosis, were examined and divided into "Good" and "Poor" CCC groups based on Rentrop Cohen classification. RNA samples were obtained from all patients, as well as from oxygen and glucose-deprived (OGD) HUVECs. PVT1, miR-15b-5p and AKT3 levels were measured with RT-qPCR or Western blot, while HUVEC migration and angiogenesis were detected by, respectively, wound-healing and tube formation assays. Luciferase reporter assay confirmed direct PVT1-miR-15b-5p binding. Increased PVT1 was found in "Good CCC" patient plasma, along with being highly expressed among OGD HUVECs; PVT1 knockdown reduced HUVEC migration, tube formation, and pro-angiogenic factor expression. Conversely, OGD HUVECs had downregulated miR-15b-5p, and miR-15b-5p overexpression significantly depressed their angiogenic capabilities. These PVT1 knockdown- or miR-15b-5p overexpression-associated reductions in angiogenic effects were reversed by AKT3 overexpression. In vivo, neovascularization and functioning in both ischemic mice hind-limbs and infarcted myocardium injected with ADV-sh-PVT1 were reduced, which were ameliorated by concurrent antagomiR-15b-5p injections. Circulating PVT1 may serve as a useful biomarker to distinguish between good versus poor CCC, as it is involved in orchestrating angiogenesis via the miR-15b-5p-AKT3 axis; it thus has potential as a target for treating ischemic disease.

High expression of long noncoding RNA plasmacytoma variant translocation 1 is an independent risk factor for recurrence after radiofrequency ablation in atrial fibrillation patients.

Atrial fibrillation (AF) is a common arrhythmia. Radiofrequency ablation (RFA) is the major AF treatment. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is related to AF diagnosis. This study explored the clinical roles of PVT1 in AF. Totally, 168 AF patients and 100 healthy controls were selected. Plasma lncRNA PVT1 in AF patients before/after RFA was detected and the diagnostic efficacy and postoperative recurrence prediction value in AF were analyzed. Effects of plasma PVT1 expression on AF recurrence and its correlation with transforming growth factor beta 1 (TGF-β1) in the recurrence and non-recurrence groups were analyzed by Pearson coefficient. The risk factors of AF recurrence were evaluated. Plasma PVT1 was highly expressed in AF patients and diminished after RFA. PVT1 level >1.255 assisted AF diagnosis. The plasma PVT1 level in the recurrence group was higher than that of the non-recurrence group. PVT1 level >1.525 assisted the prediction for postoperative recurrence. AF postoperative recurrence incidence in high PVT1 expression group was clearly higher than that in low PVT1 expression group, and plasma PVT1 expression in patients of the recurrence and non-recurrence groups was positively correlated with TGF-β1 content. High PVT1 expression was an independent risk factor for postoperative recurrence. Briefly, high PVT1 level assisted AF diagnosis and recurrence evaluation after RFA and was an independent risk factor for AF postoperative recurrence.

LncRNA PVT1 Promotes Cell Proliferation, Invasion, and Migration and Inhibits Cell Apoptosis by Phosphorylating YAP.

Gastric cancer (GC) as a serious global health problem is a threat to human longevity. Plasmacytoma variant translocation 1 (PVT1) participates in the formation and progression of various cancers, including GC. The aim of this study is to investigate the mechanism underlying the functions of PVT1 and explore a novel target for the diagnosis and treatment of GC. Analysis of the TCGA dataset using the R software identified that the lncRNA PVT1 was greatly upregulated in GC tissues. Twenty pairs of GC and adjacent normal tissues were acquired from patients with GC, and the expression of PVT1 was evaluated using RT-qPCR. Furthermore, PVT1 expression was knocked down in GC cells using siRNA, and the GC cells were divided into control, negative control (NC), and siRNA groups. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) and colony formation assays, whereas cell migration and invasion ability were investigated through wound healing and Transwell assays. Moreover, Western blotting was used to analyze the expression of Yes-associated protein (YAP) and epithelial-to-mesenchymal transition (EMT) proteins. We also found that PVT1 and YAP expressions were upregulated in the GC tissues compared with those in the adjacent nontumor tissues. Knockdown of PVT1 was found to inhibit the proliferation, invasion, and migration and promote apoptosis of GC cells. Furthermore, knockdown of PVT1 downregulated YAP and promoted phosphorylation of YAP, suggesting that PVT1 exerts actions on GC cells by targeting YAP and inhibits cell apoptosis in vitro. The EMT process was also inhibited by the knockdown of PVT1. In summary, lncRNA PVT1 facilitated cell proliferation, invasion, and migration and suppressed cell apoptosis by targeting YAP. This study suggests that the expressions of PVT1 and YAP could be used for the early detection of GC and the occurrence and development of GC could be inhibited by interfering the interaction of PVT1 and YAP, which will provide new insights for the diagnosis, treatment, and prognosis of GC.

LncRNA PVT1 contributes to invasion and doxorubicin resistance of bladder cancer cells through promoting MDM2 expression and AURKB-mediated p53 ubiquitination.

In most bladder cancer (BC) patients, cancer cells will eventually develop chemical resistance causing increased mortality. This study aimed to explore the mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating doxorubicin (ADM) resistance of BC cells. We observed that PVT1 expression was upregulated in ADM-resistant BC cells compared with ADM-sensitive BC cells. Downregulation of PVT1 suppressed ADM-resistant BC cell proliferation and invasion, promoted apoptosis, and increased sensitivity to ADM, while PVT1 overexpression promoted ADM-sensitive BC cell growth and their resistance to ADM. Further study uncovered that PVT1 could interact with and promote mouse double minute 2 (MDM2) expression, and upregulated MDM2-mediated Aurora kinase B (AURKB). Furthermore, Nutlin-3, an inhibitor of MDM2, could counteract the promotive effects of PVT1 overexpression on ADM resistance of ADM-sensitive BC cell, the expression of multidrug-resistance-related proteins, and the inhibition of p53-mediated tumor suppressor genes. And, overexpression of MDM2 or AURKB reversed the promotive effects of PVT1 silence on the ADM sensitivity of ADM-resistant BC cell, and the inhibitory effect on expression multidrug resistance proteins. Mechanically, AURKB increased MDM2-mediated p53 ubiquitination. Taken together, PVT1 promoted BC cell proliferation and drug resistance via elevating MDM2 expression and AURKB-mediated p53 ubiquitination.

Association of lncRNA PVT1 Gene Polymorphisms with the Risk of Essential Hypertension in Chinese Population

Vascular dysfunction and hyperlipidemia are essential risk factors contributing to essential hypertension (EH). The plasmacytoma variant translocation 1 (PVT1) is involved in modulating angiogenesis in tumor tissues and plays an important role in fat differentiation in the progress of obesity. Therefore, we selected two tagSNPs of PVT1 (rs10956390 and rs80177647) to investigate whether they are contributing to the risk of hypertension in Chinese patients. In total, 524 adult patients with EH and 439 matched healthy controls were enrolled for two central of China. Results. PVT1 rs10956390 and rs80177647 polymorphisms were genotyped by using TaqMan assay. PVT1 rs10956390 TT genotype was associated with a decreased risk of EH (OR = 0.561, 95% CI = 0.372-0.846, P = 0.006), while rs80177647 TA genotype was associated with an increased risk (OR = 2.236, 95% CI = 1.515-3.301, P < 0.001). Rs10956390 T allele was associated with lower triglyceride levels in the plasma both from healthy and EH donors. What is more, there is an association between rs10956390 polymorphism and HDL-C level, as well as LDL-C. Conclusion. PVT1 rs10956390 and rs80177647 polymorphisms may contribute to the risk of EH in Chinese population by regulating blood lipid levels.

Small interfering RNA-induced silencing lncRNA PVT1 inhibits atherosclerosis via inactivating the MAPK/NF-κB pathway.

Atherosclerosis (AS) is a chronic disease of the arterial wall. The role of lncRNAs in AS has been acknowledged. This study investigated the role of lncRNA plasmacytoma variant translocation 1 (PVT1) in AS via the MAPK/NF-κB pathway. Serum samples were collected from AS and non-AS patients. Serum levels of PVT1, CRP, IL-6, IL-1β, and TNF-α were determined. AS mouse model was established and transfected with si-PVT1. Levels of TG, TC, HDL, LDL, MAPK, NF-κB, MMP-2, MMP-9, TIMP-1, and macrophage content were detected. Human arterial vascular smooth muscle cells (HA-VSMCs) induced by 50 mg/mL oxLDL were transfected with si-PVT1 or oe-PVT1 and added with MAPK inhibitor U0126. Viability, apoptosis, cell cycle, colony formation and DNA replication were assessed. Levels of apoptosis-related proteins were detected. Consequently, PVT1 was highly expressed in AS patients. Silencing PVT1 decreased levels of TG, TC, LDL, IL-6, IL-1β, TNF-α, MMP-2, MMP-9, CRP, TIMP-1, MAPK, and NF-κB, increased HDL, reduced atherosclerotic plaques and macrophage content in mice, inhibited viability, clones and EdU positive rates in HA-VSMCs, but promoted apoptosis and cell cycle arrest. Inhibition of MAPK/NF-κB pathway suppressed proliferation and promoted apoptosis of HA-VSMCs while PVT1 overexpression facilitated AS development. Briefly, silencing PVT1 inhibited AS development by downregulating MAPK/NF-κB pathway.

Knockdown of lncRNA PVT1 inhibits the proliferation and accelerates the apoptosis of colorectal cancer cells via the miR‑761/MAPK1 axis.

Colorectal cancer (CRC) is associated with high morbidity rates. Long non‑coding RNAs (lncRNAs) participate in the development of CRC. However, the potential roles of lncRNA plasmacytoma variant translocation1(PVT1) in CRC remain unknown. Therefore, the aim of the present study was to investigate the potential roles of PVT1 in CRC. Reverse transcription‑quantitative PCR and western blot analyses were conducted to determine the mRNA and protein expression levels. The cellular behaviors were detected using 5‑Ethynyl‑2'‑deoxyuridine, Cell Counting Kit‑8 and flow cytometry assays. The interaction between PVT1 and microRNA (miR)‑761 or MAPK1 was confirmed using a dual‑luciferase reporter assay. Moreover, the Pearson's method was applied for correlation analysis. The results demonstrated that the expression levels of PVT1 and MAPK1 were upregulated, while miR‑761 was downregulated in CRC tissues. The expression of PVT1 was positively correlated with MAPK1 and negatively correlated with miR‑761. In addition, PVT1 sponged miR‑761 to upregulate MAPK1 expression. It was found that the knockdown of PVT1 expression inhibited the proliferation and promoted the apoptosis of CRC cells, which was more potent in cells transfected with miR‑761. The regulatory role of small interfering RNA‑PVT1 on the expression of apoptosis‑related genes was reduced by MAPK1. Collectively, the present results suggested that knockdown of PVT1 may inhibit the progression of CRC by regulating the miR‑761/MAPK1 axis, which may provide a promising biomarker for the treatment of CRC.

LncRNA PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis by miR-153-3p/GRB2 axis via ERK/p38 pathway

Background and aimsLncRNA plasmacytoma variant translocation 1 (PVT1) plays a regulatory role in some cardiovascular diseases, but its role in atherosclerosis (AS) remains barely explored. The study aimed to investigate the effects of PVT1 on high fat diet-induced AS and its potential mechanisms. Methods and resultsApoE −/− mice were fed with high fat diet for 8 weeks to establish an AS model. Lentiviral vectors containing PVT1 short hairpin RNA (PVT1-shRNA) or NC-shRNA were administered by tail vein injection. Cell viability, apoptosis, inflammatory factor secretion, and cellular oxidative stress were measured to evaluate oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm the interaction between miR-153-3p and PVT1 or growth factor receptor binding protein 2 (GRB2). Atherosclerotic lesions, lipid deposition, and cell apoptosis in aorta were analyzed by H&E, Oil Red O, and TUNEL straining. PVT1 knockdown alleviated ox-LDL-induced inflammation, apoptosis and oxidative stress in HUVECs. PVT1 acted as a sponge of miR-153-3p, and GRB2 was confirmed as a target of miR-153-3p. MiR-153-3p overexpression attenuated the enhanced effects of PVT1 on ox-LDL-induced cell damage. GRB2 overexpression reversed the mitigating effects of miR-153-3p on ox-LDL-caused injury. Inhibiting PVT1 restrained the activation of ERK1/2 and p38 pathway via miR-153-3p/GRB2 axis. Additionally, silencing PVT1 in vivo reduced atherosclerotic plaques, lipid deposition, inflammation, oxidative stress, and apoptosis in AS mice. ConclusionPVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis through miR-153-3p/GRB2 axis via ERK1/2 and p38 pathway.

LncRNA PVT1 promotes the progression of ovarian cancer by activating TGF-β pathway via miR-148a-3p/AGO1 axis.

Ovarian cancer is a lethal gynaecologic malignancy with poor diagnosis and prognosis. The long non‐coding RNA plasmacytoma variant translocation1 (PVT1) and argonaute 1 (AGO1) are associated with carcinogenesis and chemoresistance; however, the relationship between PVT1 and AGO1 and the downstream mechanisms in ovarian cancer remains poorly known. PVT1 and AGO1 expression was assessed through RT‐qPCR and Western blotting in both human tissues and cell lines. The viability and proliferation of ovarian cancer cells were determined by CCK‐8 assay and TUNEL assay in vitro and immunohistochemistry in vivo. Cell invasion and migration were investigated through transwell and wound‐healing assays. The roles and mechanisms of AGO1 on cell functions were further probed via gain‐ and loss‐of‐function analysis. We reveal that PVT1 expression was significantly increased in ovarian cancer tissues which is associated with advanced FIGO stage, lymph‐node metastasis, poor survival rate, and high expression of AGO1. PVT1 or AGO1 knockdown significantly reduced the cell viability and increased the cell apoptosis and inhibited ovarian tumour growth and proliferation. Furthermore, we discovered that PVT1 up‐regulated the expression of AGO1 and thus regulated the transforming growth factor‐β (TGF‐β) pathway to promote ovarian cancer progression through sponging miR‐148a‐3p. Additionally, the activation of ERK1/2, smad2 and smad4 is observed to be related to the PVT1/miR‐148a‐3p/AGO1/TGF‐β pathway‐induced cascades. Taken together, the present study reveals that PVT1/miR‐148a/AGO1 axis plays an important role in the progression of ovarian cancer and emphasize the potential as a target of value for ovarian cancer therapy.

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.

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 in the Pathogenesis and Clinical Management of Renal Cell Carcinoma

LncRNA PVT1 (plasmacytoma variant translocation 1) has become a staple of the lncRNA profile in patients with renal cell carcinoma (RCC). Common dysregulation in renal tumors outlines the essential role of PVT1 in the development of RCC. There is already a plethora of publications trying to uncover the cellular mechanisms of PVT1-mediated regulation and its potential exploitation in management of RCC. In this review, we summarize the literature focused on PVT1 in RCC and aim to synthesize the current knowledge on its role in the cells of the kidney. Further, we provide an overview of the lncRNA profiling studies that have identified a more or less significant association of PVT1 with the clinical behavior of RCC. Based on our search, we analyzed the 17 scientific papers discussed in this review that provide robust support for the indispensable role of PVT1 in RCC development and future personalized therapy.

Contribution of lncRNA CASC8, CASC11, and PVT1 Genetic Variants to the Susceptibility of Coronary Heart Disease.

The purpose of this study was to explore the relationship between lncRNA CASC8, CASC11, and plasmacytoma variant translocation 1 (PVT1). genetic variants and coronary heart disease (CHD) susceptibility among a Chinese Han population. Five single nucleotide polymorphisms were genotyped by Agena MassARRAY platform among 464 CHD patients and 510 healthy controls. Binary logistic regression models by calculating odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between selected single nucleotide polymorphisms and CHD risk. Multifactor dimensionality reduction analysis was performed to analyze gene-gene interaction. PVT1 rs4410871 (OR = 0.77, P = 0.040) was associated with a reduced risk of CHD occurrence in the Chinese population. CASC11 rs9642880 (OR = 1.49, P = 0.021) was a risk factor for increased CHD susceptibility in subjects over 60 years old, and PVT1 rs4410871 was a protective factor for CHD susceptibility in males (OR = 0.67, P = 0.015) and smokers (OR = 0.62, P = 0.047). Complications (hypertension or diabetes) of CHD influenced the association between CASC8, CASC11, and PVT1 genetic polymorphisms and CHD predisposition. Moreover, CASC8, CASC11, and PVT1 polymorphisms were related to the number of pathological branches and Gensini score in CHD patients. The study displayed the contribution of CASC8, CASC11, and PVT1 genetic polymorphisms to CHD predisposition, and these variants could serve as potential biomarkers of CHD susceptibility. These findings contribute to enhancing the understanding of the role of lncRNA polymorphisms in CHD risk.

Salvianolic Acid A Protects H9C2 Cardiomyocytes from Doxorubicin-Induced Damage by Inhibiting NFKB1 Expression Thereby Downregulating Long-Noncoding RNA (lncRNA) Plasmacytoma Variant Translocation 1 (PVT1).

BackgroundA cardioprotective effect of salvianolic acid A (SalA) has been described, but it is unknown whether SalA can protect cardiomyocytes against doxorubicin (Dox)-induced cardiotoxicity. This study aimed to investigate whether SalA could inhibit Dox-induced apoptosis in H9C2 cells and to uncover the potential mechanism.Material/MethodsH9C2 cardiomyocytes exposed to Dox were treated with SalA or not, and then cell viability, apoptosis, and the expression of nuclear factor-κB (NF-κB) signaling were detected by Cell Counting Kit-8, TUNEL staining, and western blot assays, respectively. Nuclear factor kappa B subunit 1 (NFKB1) was overexpressed in H9C2 cells, and then alterations in cell viability and apoptosis in H9C2 cells co-treated with Dox and SalA were investigated.ResultsSalA (2, 10, and 50 μM) had no effect on H9C2 cell viability, while Dox reduced cell viability in a concentration-dependent manner. In addition, SalA rescued Dox-decreased cell viability. Dox also triggered apoptosis as evidenced by an increased ratio of TUNEL-positive cells, enhanced expression of pro-apoptotic proteins, and reduced expression of anti-apoptotic protein BCL-2, which were all partially blocked by SalA co-treatment. The proteins involved in NF-κB signaling including IκBα, IKKα, IKKβ, and p65 were activated by Dox but inactivated by SalA co-treatment. Moreover, Dox increased NFKB1 mRNA and nuclear expression, which was blocked by SalA. NFKB1 could bind to plasmacytoma variant translocation 1 (PVT1) and upregulate PVT1 expression. Mechanistically, the overexpression of NFKB1 blocked the inhibitory effect of SalA on Dox-induced cell viability impairment and apoptosis.ConclusionsWe demonstrated that SalA may exert a protective effect against Dox-induced H9C2 injury and apoptosis via inhibition of NFKB1 expression, thereby downregulating lncRNA PVT1.

The effects of LncRNA PVT1 on clinical characteristics and survival in breast cancer patients: A protocol for systematic review and meta analysis.

Background:Currently, an increasing number of long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human carcinomas and play a vital role in tumourigenesis. Some studies were carried out to investigate the influence of the expression of plasmacytoma variant translocation 1 (PVT1) on prognosis and its clinical significance in patients with breast cancer, while the results were contradictory and uncertain. A meta-analysis was conducted with controversial data to accurately assess the issue.Methods:A detailed search of relevant researches was performed in Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science. Two reviewers independently conducted data extraction and literature quality evaluation. Odd ratio and its 95% confidence intervals were applied to evaluate the relationship between PVT1 and clinicopathological characteristics of breast cancer patients. Hazard ratios and its 95% confidence intervals were adopted to assess the prognostic effects of PVT1 on overall survival and disease-free survival. Meta-analysis was conducted with Stata 14.0 softwareResults:This study will provide high-quality evidence-based medical evidence for the correlation between PVT1 expression and overall survival, and disease-free survival and clinicopathological features.Conclusion:The study will provide updated evidence to evaluate whether the expression of PVT1 is in association with poor prognosis in patients with breast cancer.OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/C2TYE.