Non-coding RNA Plasmacytoma Variant Translocation Research Articles

LncRNA PVT1 induces chondrocyte apoptosis through upregulation of TNF-α in synoviocytes by sponging miR-211-3p

Temporomandibular joint osteoarthritis (TMJ OA) is an important subtype of temporomandibular disorders (TMD). Articular cartilage destruction is considered a common pathological feature of TMJ OA, which is reported to be mainly induced by chondrocyte apoptosis. Synovial sterile inflammation is an initial factor of TMJ OA-associated articular cartilage destruction. Therefore, determining the mechanism of synovial membrane inflammation-induced articular cartilage destruction in TMJ OA is important for the TMJ OA therapy. In this study, we detected the function of synoviocytes in chondrocyte apoptosis under lipopolysaccharide (LPS)-induced inflammatory conditions and explored the underlying mechanism. We found that synoviocytes in inflammatory conditions facilitated LPS-induced chondrocytes apoptosis by secreting increased Tumor Necrosis Factor α (TNF-α), which was induced by long non-coding RNA plasmacytoma variant translocation 1 (PVT1) upregulation. PVT1 served as a competing endogenous RNA that sponged the microRNA miR-211-3p and prevented the inhibition of TNF-α expression. In conclusion, our in vitro study revealed that PVT1 has a previously unknown role in chondrocyte apoptosis, which may also be a mechanism underlying synoviocyte involvement in TMJ OA.

LncRNA PVT1 Promotes Tumorigenesis of Colorectal Cancer by Stabilizing miR-16-5p and Interacting with the VEGFA/VEGFR1/AKT Axis

Recently, the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was reported to be involved in the pathogenesis of several cancers, including human colorectal cancer (CRC). However, the molecular basis for cancer initiation, development, and progression remains unclear. In this study, we observe that upregulated PVT1 is associated with poor prognosis and bad clinicopathological features of CRC patients. In vitro means of PVT1 loss in a CRC cell line inhibit cell proliferation, migration, and invasion. Furthermore, dual-luciferase reporter and RNA pull-down assays indicated that PVT1 binds to miR-16-5p, which has been shown to play strong tumor suppressive roles in CRC. Targeted loss of miR-16-5p partially rescues the suppressive effect induced by PVT1 knockdown. Vascular endothelial growth factor A (VEGFA), a direct downstream target of miR-16-5p, was suppressed by PVT1 knockdown in CRC cells. Overexpression of VEGFA is known to modulate the AKT signaling cascade by activating vascular endothelial growth factor receptor 1 (VEGFR1). We, therefore, show that PVT1 loss combined with miR-16-5p overexpression reduces tumor volume maximally when propagated within a mouse xenograft model. We conclude that the PVT1-miR-16-5p/VEGFA/VEGFR1/AKT axis directly coordinates the response in CRC pathogenesis and suggest PVT1 as a novel target for potential CRC therapy.

Long noncoding RNA PVT1 contributes to vascular endothelial cell proliferation via inhibition of miR-190a-5p in diagnostic biomarker evaluation of chronic heart failure.

Long noncoding RNAs (lncRNAs) and microRNAs (miRs) serve critical roles in various cellular processes and can be used as noninvasive biomarkers in human diseases. The present study aimed to investigate the effects of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-190a-5p on vascular endothelial cell (EC) proliferation and assess their clinical value in the diagnosis of chronic heart failure (CHF). The expression of PVT1 and miR-190a-5p was investigated using reverse transcription-quantitative PCR. The interaction between PVT1 and miR-190a-5p was confirmed using a luciferase reporter assay. A Cell Counting Kit-8 assay was performed to examine EC proliferation. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of PVT1 and miR-190a-5p. PVT1 directly decreased the expression of miR-190a-5p in ECs. Overexpression of miR-190a-5p in ECs led to inhibited cell proliferation and miR-190a-5p antagonized the promotive effect of PVT1 on EC proliferation. Serum expression of PVT1 increased, while serum expression of miR-190a-5p decreased in patients with CHF compared with healthy controls (all P<0.001). The ROC curves indicated that PVT1 and miR-190a-5p were two diagnostic biomarkers of CHF, and the combination of PVT1 and miR-190a-5p showed better diagnostic accuracy compared with using PVT1 or miR-190-5p alone. In conclusion, the present study demonstrated that PVT1 promoted EC proliferation by directly suppressing miR-190a-5p. Circulating PVT1 and miR-190a-5p are possible two candidate diagnostic biomarkers of CHF, and the combined detection of the two indicators may provide a novel approach for CHF diagnosis.

UPF1 Participates in the Progression of Endometrial Cancer by Inhibiting the Expression of lncRNA PVT1.

BackgroundEndometrial carcinoma (EC) is the primary cause of death associated with cancer globally. Thus, the possible molecular mechanism of EC needs further exploration. Up-frameshift protein 1 (UPF1) is an ATPase depending on RNA/DNA and RNA helicase depending on ATP. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was dysregulated in diverse diseases.MethodsqRT-PCR and Western blot were applied to detect UPF1 and PVT1 in EC. CCK-8, colony formation, and Transwell assays were used to test the effects of UPF1/PVT1 on cell proliferation and migration. Cells were cultured with actinomycin D to observe mRNA stability, and RNA immunoprecipitation assay was applied to verified the relationship between UPF1 and PVT1. Glucose consumption and lactate generation were measured when cells were transfected with siRNA.ResultsResults demonstrated that the expression of UPF1 exhibited a remarkable decrement in EC tissues relative to that in non-tumor tissues. Subsequent functional experiments suggested that UPF1 decrement stimulated EC cells to grow and migrate. Moreover, UPF1 was discovered to be linked to PVT1 and had an inverse correlation with PVT1. Besides, PVT1 expression affected EC growth and migration, and PVT1 decrement alleviated the influence of UPF1 decrement on EC growth and migration and strengthened glycolysis in EC.ConclusionIn this study, we found that UPF1 was down-regulated in EC tissues, and UPF1 might exert its role by regulating the expression of PVT1.

LncRNA PVT1 regulates gallbladder cancer progression through miR-30d-5p.

Gallbladder cancer (GBC) is a malignant tumors that develops insidiously and rapidly. In this work, we explored the function of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) in modulating GBC development. PVT1 and miR-30d-5p expression were detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The relationship of PVT1 and miR-30d-5p was analyzed by Dual luciferase activity and Spearman correlation analysis. The effect of PVT1 on GBC progression was detected by cell counting kit-8 (CCK-8) and Transwell assay. In GBC tissues and cell lines, upregulation of PVT1 and downregulation of miR-30d-5p were observed. PVT1 silencing suppressed cell proliferation and invasion of GBC cells. Based on the analysis of Dual luciferase activity and Spearman correlation, miR-30d-5p was confirmed as a target of PVT1, and their expression had a negative correlation in GBC tissues. Additionally, miR-30d-5p inhibitor could reverse the effects of PVT1 knockdown. These data demonstrated that PVT1 facilitated to GBC tumorigenesis by promoting cell proliferation and invasion via miR-30d-5p, indicating that PVT1 may be a potential biomarker of GBC diagnosis and treatment.

C-Myc-activated long non-coding RNA PVT1 enhances the proliferation of cervical cancer cells by sponging miR-486-3p.

Cervical cancer is one of the most prevalent gynecological malignancies. Although the functions of long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and c-Myc in tumorigenesis have been acknowledged, the roles of c-Myc and lncRNA-PVT1 in the proliferation of cervical cancer are still unclear. Our study is designed to demonstrate the regulatory network involving c-Myc and lncRNA-PVT1 in cervical cancer. Quantitative real-time PCR and western blot assays were performed in our research to estimate the expression levels of RNA and proteins. CCK8 assays were applied to demonstrate the viability of HeLa and SiHa cells. Immunofluorescence assay was then used to investigate the co-localization of lncRNA-PVT1 and miR-486-3p. Binding of c-Myc to the promoter region of PVT1 was identified by ChIP-assay. Functionally, upregulation of lncRNA-PVT1 enhanced the proliferation and viability of cervical cancer cells. Mechanistically, lncRNA-PVT1 sponged miR-486-3p and released its repression of extracellular matrix protein 1. Besides, c-Myc functioned as an activator of lncRNA-PVT1 and upregulated its expression by binding to the promoter of PVT1 in cervical cancer cells. lncRNA-PVT1 was upregulated by c-Myc and thus enhanced the proliferation of cervical cancer cells by sponging miR-486-3p.

Knockdown of long non-coding RNA plasmacytoma variant translocation 1 inhibits cell proliferation while promotes cell apoptosis via regulating miR-486-mediated CDK4 and BCAS2 in multiple myeloma.

This study aimed to investigate the effect of long non-coding RNA-plasmacytoma variant translocation 1 (lnc-Pvt1) knockdown on regulating cell proliferation and apoptosis, and to explore its molecular mechanism in multiple myeloma (MM). Lnc-Pvt1 expression was detected in MM cell lines (NCI-H929, U-266, LP-1 and RPMI-8226 cell lines) and human normal plasma cells. In U-266 cells and LP-1 cells, control shRNA and lnc-Pvt1 shRNA plasmids were transferred. Rescue experiments were further performed by transfection of lnc-Pvt1 shRNA alone and lnc-Pvt1 shRNA and miR-486 shRNA plasmids. Cells proliferation, apoptosis, RNA expression, and protein expression were determined by cell counting kit-8, annexin V-FITC-propidium iodide, quantitative polymerase chain reaction, and Western blot assays, respectively. Lnc-Pvt1 expression was increased in MM cell lines (NCI-H929, U-266 and LP-1 cell lines) compared with human normal plasma cells. In U-266 cells, lnc-Pvt1 shRNA suppressed cell proliferation while enhanced cell apoptosis compared with control shRNA. Also, lnc-Pvt1 shRNA increased miR-486 expression compared with control shRNA. Further rescue experiment revealed that miR-486 shRNA did not change lnc-Pvt1 level, but increased CDK4 and BCAS2 expressions in lnc-Pvt1 knockdown-treated cells. In addition, miR-486 shRNA promoted cell proliferation while inhibited cell apoptosis in lnc-Pvt1 knockdown-treated cells. These results were further validated in LP-1 cells. Lnc-Pvt1 knockdown inhibits cell proliferation and induces cell apoptosis through potentially regulating miR-486-mediated CDK4 and BCAS2 in MM.

Long Noncoding RNA Plasmacytoma Variant Translocation 1 Is Increased in Multiple Myeloma and Correlates With Lower Induction Response

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.

Long non-coding RNA PVT1 regulates glioma proliferation, invasion, and aerobic glycolysis via miR-140-5p.

To investigate the regulation of long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) on proliferation, invasion, and aerobic glycolysis in glioma cells via miR-140-5p. Sixty patients with glioma treated in our hospital were recruited. The expression of PVT1 in tissues and cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the effects on the prognosis were observed. Glioma cell lines U87 and T98MG were either stably or transiently transfected with over-expression or inhibition vectors. Cell counting kit-8 (CCK-8), transwell, glucose, and lactate detection were employed to measure cell proliferation, invasion, and aerobic glycolysis after transfection. The correlation between PVT1 and miR-140-5p was determined by Dual-Luciferase reporter assay. RNA pull-down and RNA immunoprecipitation (RIP) test were adopted to indicate the correlation between PVT1 and miR-140-5p. PVT1 was highly expressed and had superior diagnostic value in gliomas, and the high expression of PVT1 resulted in poor prognosis of patients. Over-expressing PVT1 increased cell proliferation, invasion, and aerobic glycolysis, while inhibiting PVT1 yielded opposite outcome. Dual-Luciferase reporter assay confirmed that PVT1 could target miR-140-5p. Functional analysis showed that over-expression of miR-140-5p inhibited proliferation, invasion, and aerobic glycolysis in glioma cells. Rescue experiment found that the inhibitory effect of miR-140-5p could be eliminated by up-regulating PVT1 expression. PVT1 promotes proliferation, invasion, and aerobic glycolysis in glioma cells by regulating miR-140-5p.

Long Non-Coding RNA PVT1 Regulates BAMBI To Promote Tumor Progression In Non-Small Cell Lung Cancer By Sponging miR-17-5p.

BackgroundNon-small cell lung cancer (NSCLC) is a common malignancy over the world. Previous report indicated that the plasmacytoma variant translocation 1 (PVT1) has been documented to function as an oncogene in various types of human cancers. However, the biological mechanism of PVT1 was still rarely reported in NSCLC.MethodsThe levels of PVT1, miR-17-5p, and bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) in NSCLC tissues (n=64) and cells (H1299 and A549) were detected by qRT-PCR and immunohistochemistry (IHC). The protein level of BAMBI was measured by Western blot assay. Cell viability and apoptotic rate were evaluated by MTT assay and flow cytometry, respectively. The migrated and invaded abilities were assessed by Transwell assay and Wound healing assay. The interactions between miR-17-5p and PVT1 or BAMBI were predicted by starBase v2.0 and TargetScan, respectively, and then dual-luciferase reporter assay and RNA pull-down assay were performed to verify these interactions. The mice model experiments were constructed to further validate the roles of PVT1 in vivo.ResultsThe levels of PVT1 and BAMBI were both apparently increased, and miR-17-5p was declined in NSCLC tissues and cells. The depletion of PVT1 or BAMBI blocked cell viability, migrated and invaded abilities but impelled apoptotic rate in A549 and H1299 cells. PVT1 was validated as a sponge to miR-17-5p and BAMBI was a direct target of miR-17-5p. PVT1 promoted cell viability, migrated and invaded abilities but repressed apoptotic rate by targeting BAMBI. MiR-17-5p regulated cell behaviors mediated by PVT1. PVT1 silencing decreased BAMBI expression by sponging miR-17-5p. In addition, PVT1 knockdown blocked the xenograft tumor growth in vivo.ConclusionThese results manifested that PVT1 modulated BAMBI to promote tumor progression in NSCLC by sponging miR-17-5p. Thus, the novel regulatory pathway may provide a new therapeutic target for NSCLC patients.

Knockdown of PVT1 inhibits IL-1β-induced injury in chondrocytes by regulating miR-27b-3p/TRAF3 axis

Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been identified to implicate in the progression of osteoarthritis (OA). However, the mechanism underlying PVT1 in OA development remains largely unknown. This study aimed to investigate the effect of PVT1 on interleukin-1 beta (IL-1β)-induced injury in chondrocytes and explore potential mechanism. The cartilage tissues from 25 OA patients and normal controls were collected. Human transformed chondrocytes C28/I2 were stimulated by IL-1β. The levels of PVT1, microRNA (miR)-27b-3p, and tumor necrosis factor receptor-associated factor 3 (TRAF3) were detected by quantitative real-time polymerase chain reaction or western blot. IL-1β-induced injury was investigated by cell viability, apoptosis, autophagy and inflammatory response using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, flow cytometry, western blot and enzyme linked immunosorbent assay, respectively. The target association between miR-27b-3p and PVT1 or TRAF3 was explored by luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. We found that PVT1 expression was enhanced in OA patients and IL-1β-treated C28/I2 cells. Silence of PVT1 promoted cell viability and autophagy but suppressed apoptosis and inflammatory response in IL-1β-treated C28/I2 cells. miR-27b-3p was confirmed as a target of PVT1 and its deficiency reversed the suppressive effect of PVT1 knockdown on IL-1β-induced injury. TRAF3 was a target of miR-27b-3p and attenuated the effect of miR-27b-3p on IL-1β-induced injury in C28/I2 cells. Moreover, TRAF3 expression was positively regulated by PVT1 via sponging miR-27b-3p. Collectively, knockdown of PVT1 increased cell viability and autophagy but inhibited apoptosis and inflammatory response in chondrocytes treated by IL-1β via up-regulating miR-27b-3p and down-regulating TRAF3.

RETRACTED: Silencing lncRNAs PVT1 Upregulates miR-145 and Confers Inhibitory Effects on Viability, Invasion, and Migration in EC

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is correlated to various malignant tumors. Consequently, we explored effects of lncRNA PVT1 on esophageal carcinoma (EC) targeting microRNA-145 (miR-145). EC tissues, adjacent normal tissues, and EC-related cell lines were collected and cultured. Expression of lncRNA PVT1, miR-145, fascin-1 (FSCN1), and related genes with intervening expression of PVT1 and miR-145 was determined. Bioinformatic website, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) were carried to verify target relationship among lncRNA PVT1, FSCN1, and miR-145. Scratch test, Transwell assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry were performed for detection of migration, invasion, viability, and apoptosis of transfected cells, respectively. Finally, tumor formation in nude mice was measured. After database analysis, lncRNA PVT1, miR-145, and FSCN1 were selected for study. lncRNA PVT1 and FSCN1 can bind to miR-145. After overexpressing miR-145 or inhibiting lncRNA PVT1, EC cell viability, migration, and invasion were inhibited, while volume and weight of tumor formation in nude mice decreased. Expression of lncRNA PVT1, FSCN1, Bcl-2, CD147, VEGFR2, and MTA1 decreased and expression of miR-145 and Bax increased. Silencing lncRNA PVT1 can upregulate miR-145, which is a tumor suppressor in EC via knockdown of FSCN1. Thus, we might provide a potential theoretical basis for EC treatment.

LncRNA PVT1 Overexpression Improves Premature Ovarian Insufficiency by Inhibiting Granulosa Cell Apoptosis

Background: Long noncoding RNA PVT1 (plasmacytoma variant translocation 1) is aberrantly expressed in a variety of cancers. However, whether PVT1 is aberrantly expressed in granulosa cells from premature ovarian insufficiency (POI) patients and the role of PVT1 in POI is largely unknown. Methods: The interaction between PVT1 and Foxo3a was confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. Methylation level in PVT1 promoter region was detected by methylation-specific PCR. The subcellular location of PVT1 was detected by FISH assay. Granulosa cell apoptosis was detected using flow cytometry. The effect of PVT1 on the transcriptional activity of Foxo3a was detected by luciferase reporter assay. Results: PVT1 was down-regulated in ovarian tissues of POI group than control group, which was regulated by high methylation level. PVT1 was mainly localized in cytoplasm of granulosa cells. In addition, we determined PVT1 interacted with Foxo3a, down-regulation of PVT1 inhibited Foxo3a phosphorylation, resulting in the suppression of Foxo3a degradation and the increase of Foxo3a transcriptional activity. Moreover, down-regulation of PVT1 promoted granulosa cell apoptosis through Foxo3a. Finally, in vivo experiment showed that overexpression of PVT1 restored ovarian function in POI mice. Conclusion: Down-regulation of PVT1 inhibits Foxo3a phosphorylation that suppresses its degradation and activates the transcriptional activity of Foxo3a, thereby promoting granulosa cell apoptosis in POI. Funding Statement: This study was supported by International (Regional) Cooperation and Exchange (ICE) Projects of the National Natural Science Foundation of China (NSFC) (Grant No. 81820108016), Clinical Medical Research Fund of Chinese Medical Association-Reproductive Medicine Research and Development Projects for Youth Grant: Application study of human fetal primordial germ cells to oocyte differentiation and development in vitro (Grant No. 17020210690), and Henan Provincial Science and Technology Project: Study on the mechanism of meiosis initiation induced by human primordial germ cells to oocytes in vitro (Grant No. 182102310139). Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Clinical Research Ethics Committee of the first affiliated hospital of Zhengzhou University (Ethical review number: 2019-KY-158). Written informed consents were obtained from all the patients involved. The animal experiment was approved by the Ethics Committee of the first affiliated hospital of Zhengzhou University.

Long Non-Coding RNA Plasmacytoma Variant Translocation 1 (PVT1) Enhances Proliferation, Migration, and Epithelial-Mesenchymal Transition (EMT) of Pituitary Adenoma Cells by Activating β-Catenin, c-Myc, and Cyclin D1 Expression.

BackgroundAs a kind of benign tumor, pituitary adenomas have attracted increasing attention from researchers. The plasmacytoma variant translocation 1 (PVT1) is a molecule in the lncRNA family protein that has been proven to play critical roles in many cancers; however, no study has explored the special biological roles of PVT1 in pituitary adenoma.Material/MethodsThe qRT-PCR assay was conducted to evaluate PVT1 expressions in various cell lines and tissues. Loss of function assays were carried out to detect the influence of silenced PVT1 on the proliferation, migration, and epithelial-mesenchymal transition (EMT) of pituitary adenoma cells. Western blotting was used to identify correlation between β-catenin and PVT1.ResultsThe PVT1 expressions were significantly enhanced in tissues of pituitary adenoma and cancer cells. Cell migration and proliferation were inhibited when the PVT1 gene was knocked down. Knockdown of PVT1 repressed the migration and EMT of pituitary adenoma cells. The PVT1 downregulation obviously blocked Wnt/β-catenin signaling pathway activity. PVT1 aggravated progression of pituitary adenoma through initiating the Wnt/β-catenin signaling pathway.ConclusionsPVT1 exerts an oncogenic role through activating Wnt/β-catenin signaling in pituitary adenoma cells. The present results may provide a potential therapeutic target or approach for treating pituitary adenomas.

Long-Chain Noncoding RNA PVT1 Gene Polymorphisms Are Associated with the Risk and Prognosis of Colorectal Cancer in the Han Chinese Population.

Background: To investigate the association between long-chain noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) gene polymorphisms and the risk and prognosis of colorectal cancer (CRC) in the Han Chinese population. Methods: A cohort of 225 Han Chinese CRC patients and 225 healthy controls was analyzed for the PVT1 gene genotypes at the loci rs1221464062, rs1366023633, rs1252200336, and rs1273526412. The levels of PVT1 mRNA, hsa-miR-455-5p, and hsa-miR-455-3p in both cancerous tissues and paracancerous normal tissues of the CRC patients were determined by reverse transcription polymerase chain reaction. The survival rate of CRC patients was recorded after 3 years of follow-up. Results: The risk of developing CRC in subjects with the ID genotype of the PVT1 gene locus rs1252200336 was 2.71 times higher compared with the type II genotype; and the D allele was a risk factor for CRC. The survival of CRC patients with the ID/DD genotypes of the PVT1 gene rs1252200336 locus was significantly lower compared with the II genotype. In both the cancerous tissues and the paracancerous normal tissues of CRC patients, the level of lncRNA PVT1 was negatively correlated with the hsa-miR-455-5p and hsa-miR-455-3p levels. In subjects carrying the ID/DD genotypes of the PVT1 gene rs1252200336 locus, the level of the lncRNA PVT1 in cancerous tissues was significantly higher compared with the II genotype, whereas the hsa-miR-455-3p level was significantly lower compared with the II genotype. Conclusion: The PVT1 gene rs1252200336 locus polymorphisms are associated with the risk of developing CRC in the Han Chinese population. The rs1252200336 locus deletion mutation (D) may impact the binding of hsa-miR-455-5p to the lncRNA PVT1 and its role in the development and progression of CRC.

Down-regulation of long noncoding RNA PVT1 inhibits esophageal carcinoma cell migration and invasion and promotes cell apoptosis via microRNA-145-mediated inhibition of FSCN1.

Accumulating evidence has established that long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is a tumor regulator in many cancers. Here, we aimed to investigate the possible function of lncRNA PVT1 in esophageal carcinoma (EC) via targeting of microRNA‐145 (miR‐145). Initially, microarray‐based gene expression profiling of EC was employed to identify differentially expressed genes. Moreover, the expression of lncRNA PVT1 was examined and the cell line presenting with the highest level of lncRNA PVT1 expression was selected for subsequent experiments. We then proceeded to examine interaction among lncRNA PVT1, FSCN1, and miR‐145. The effect of lncRNA PVT1 on viability, migration, invasion, apoptosis, and tumorigenesis of transfected cells was examined with gain‐of‐function and loss‐of‐function experiments. We observed that lncRNA PVT1 was robustly induced in EC. lncRNA PVT1 could bind to miR‐145 and regulate its expression, and FSCN1 is a target gene of miR‐145. Overexpression of miR‐145 or silencing of lncRNA PVT1 was revealed to suppress cell viability, migration, and invasion abilities, while also stimulating cell apoptosis. Furthermore, our in vivo results showed that overexpression of miR‐145 or silencing of lncRNA PVT1 resulted in decreased tumor growth in nude mice. In conclusion, our research reveals that down‐regulation of lncRNA PVT1 could potentially promote expression of miR‐145 to repress cell migration and invasion, and promote cell apoptosis through the inhibition of FSCN1. This highlights the potential of lncRNA PVT1 as a therapeutic target for EC treatment.

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1

The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1 or the overexpression of FOXA1 relieved the damage and inhibited the apoptosis of podocytes in DN, as was evidenced by the upregulated expression of synaptopodin and podocin, higher expression of Bcl-2, and lower expression of Bax and cleaved caspase-3. The key findings of this study collectively indicate that the suppression of lncRNA PVT1 exerts inhibitory effects on podocyte damage and apoptosis via FOXA1 in DN, which is of clinical significance.

Long non‑coding RNA plasmacytoma variant translocation 1 gene promotes the development of cervical cancer via the NF‑κB pathway.

The long noncoding RNA plasmacytoma variant translocation 1 gene (LncRNA PVT1) has an important role in tumor occurrence and development, yet the role and underlying molecular mechanisms of this RNA in cervical cancer have not yet been elucidated. In the present study, three cervical cancer cell lines (HeLa, Ca Ski and SiHa) were used to verify how LncRNA PVT1 mediates cervical cancer development, and the H8cell line was used as a control. A LncRNA PVT1 overexpression vector or small interfering RNAs targeting LncRNA PVT1 were transfected into cervical cancer cells to generate LncRNA PVT1 overexpression and silencing in these cells. LncRNA PVT1 overexpression accelerated the growth of cervical cancer cells by advancing the cell cycle and inhibiting cellular apoptosis; increases in Cyclin D1 (CCND1) mRNA and activated Bcl‑2 protein expression levels also supported this finding. Furthermore, NF‑κB activation and expression was increased by LncRNA PVT1 overexpression. In addition, NF‑κB activation or inhibition induced changes in cell viability, accompanied by changes in CCND1 and Bcl‑2 expression. Increases or decreases in microRNA‑16 (miR‑16) expression (using miR mimics and inhibitors) also corresponded to changes in LncRNA PVT1 expression, invitro. miR‑16 mimics and inhibitor had opposite effects to those of NF‑κB activity, and miR‑16 was demonstrated to directly interact with the NF‑κB gene as measured using the dual‑luciferase assay. In summary, LncRNA PVT1 inhibits the effect of miR‑16, promoting the cell cycle and inhibiting cellular apoptosis of cervical cancer cells, potentially via the NF‑κB pathway. The data from the present study will contribute to the current knowledge surrounding the theoretical basis of cervical cancer and provide a new perspective for the treatment of cervical cancer.

Long non-coding RNA PVT1 knockdown suppresses fibroblast-like synoviocyte inflammation and induces apoptosis in rheumatoid arthritis through demethylation of sirt6

BackgroundAs a type of chronic autoimmune joint disease, rheumatoid arthritis (RA) is a disorder, characterized by a variety of physical symptoms as well as RA fibroblast-like synoviocyte (RA-FLS) proliferation. More recently, long non-coding RNAs (lncRNAs) have been implicated in the progression of various diseases including the progression of RA. Hence, the aim of the current study was to investigate the role by which the lncRNA, plasmacytoma variant translocation 1 (PVT1), influences RA-FLSs and its ability to modulate the methylation of sirtuin 6 (sirt6).MethodsRA rat models were initially established to determine the expression of PVT1 and sirt6 in synovial tissues and RA-FLSs. Elevation or depletion of PVT1 or sirt6 was achieved by means of transformation with plasmids in order to investigate their effects on RA-FLS proliferation, inflammation and apoptosis. The localization of PVT1 and its binding ability to the sirt6 promoter region were also explored in an attempt to elucidate the correlation between PVT1 and sirt6 methylation.ResultsHigh expression of PVT1 and low expression of sirt6 were detected in the synovial tissues and RA-FLSs of the rat models. RA-FLSs treated with sh-PVT1 or oe-sirt6 exhibited suppressed cell proliferation, inflammation and induced apoptosis. PVT1 was predominately localized in the nucleus while evidence was obtained indicating that it could bind to the sirt6 promoter to induce sirt6 methylation, thus inhibiting sirt6 transcription. PVT1 knockdown was observed to restore sirt6 expression through decreasing sirt6 methylation, thereby alleviating RA.ConclusionThe key findings of the study provide evidence suggesting that, PVT1 knockdown is able to restrain RA progression by inhibiting sirt6 methylation to restore its expression.

Knockdown of long non-coding RNA PVT1 inhibits the proliferation of Raji cells through cell cycle regulation.

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been reported to be associated with oncogenesis. However, the functional role of PVT1 in Burkitt lymphoma has not yet been addressed. The purpose of the present study was to investigate the effect of PVT1 knockdown by small interfering RNA (siRNA) on the proliferation of Burkitt lymphoma Raji cells and to explore its possible mechanism of action. An effective siRNA targeting PVT1 was screened and the corresponding short hairpin RNA (shRNA) was reconstructed into a lentiviral vector. Cell proliferation and cell cycle distribution were assessed by Cell Counting kit-8 assay and flow cytometry, respectively. Protein expression levels of c-Myc, cyclin-dependent kinase inhibitor1A (CDKN1A, P21) and cyclin E1 (CCNE1) were detected by western blotting. A polymerase chain reaction (PCR) array was used to analyse the expression of genes associated with the cell cycle. PVT1 knockdown markedly suppressed proliferation, and induced cell cycle arrest at the G0/G1 phase in Raji cells. Protein expression levels of c-Myc and CCNE1 were reduced, whereas P21 protein expression was markedly increased following downregulation of PVT1 in Raji cells. The cell cycle PCR array revealed that 54 genes were upregulated and 26 genes were downregulated in Raji cells following PVT1 knockdown. Reverse transcription-quantitative PCR demonstrated that cyclin G2 (CCNG2), CDKN1A, Retinoblastoma-like 2 (RBL2, p130), HUS1 checkpoint homolog, cyclin dependent kinase inhibitor 3 (CDKN3) and cyclin dependent kinase inhibitor 1B (CDKN1B) expression were upregulated, whereas the expression levels of CCNE1, cyclin D1 (CCND1) and cell division cycle 20 (CDC20) were downregulated in Raji cells with PVT1 knockdown. In conclusion, PVT1 knockdown may inhibit the proliferation of Raji cells by arresting cells in G0/G1 phase. Furthermore, inhibition of cell proliferation may be associated with a reduction inc-Myc expression and alterations in the expression levels of cell cycle-associated genes.