Plasmacytoma Variant Translocation 1 Expression Research Articles

Downregulation of lncRNA PVT1 expression inhibits proliferation and migration by regulating p38 expression in prostate cancer.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been reported to be overexpressed in prostate cancer cells and associated with tumorigenesis in various types of cancer. However, the biological function of lncRNA PVT1 remains largely unknown. The aim of the present study was to investigate the effect of lncRNA PVT1 expression on the proliferation and migration of prostate cancer cells. Stably transfected prostate cancer cells with downregulated expression of lncRNA PVT1 were constructed by an efficient siRNA fragment, followed by confirmation by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferation was assessed using CCK-8, colony formation and xenograft assays, and cell migration was evaluated using a wound healing assay. The PathScan® Intracellular Signaling Array kit was utilized to explore the underlying molecular mechanisms of lncRNA PVT1 expression in prostate cancer cells. RT-qPCR results confirmed that the lncRNA PVT1 expression level was successfully knocked down in prostate cancer cells. When lncRNA PVT1 expression was downregulated in prostate cancer cells, proliferation and migration were significantly inhibited, compared with the control lncRNA PVT1 group. Furthermore, PVT1 knockdown decreased the phosphorylation of p38 in DU145 cells. Therefore, the present study demonstrated that lncRNA PVT1 downregulation inhibits the proliferation and migration of prostate cancer cells, and is associated with p38 phosphorylation.

Long non-coding RNA PVT1 promotes malignancy in human endometrial carcinoma cells through negative regulation of miR-195-5p

The plasmacytoma variant translocation 1 (PVT1)11PVT1: plasmacytoma variant translocation 1. gene is a long non-coding RNA (lncRNA)22lncRNA: long non-coding RNA. that has been shown to be an oncogene in many cancers. Herein, the function and potential molecular mechanisms connecting PVT1 and miR-195-5p were elucidated in endometrial cancer cell lines. Quantitative real-time PCR and fluorescence in situ hybridization (FISH)33FISH: fluorescence in situ hybridization. demonstrated that PVT1 is up-regulated concomitant with miR-195-5p down-regulation in human endometrial carcinoma tissues. PVT1 knockdown inhibited cell proliferation, migration, and invasion while facilitating apoptosis of endometrial cancer cells. Moreover, restoration of miR-195-5p due to PVT1 knockdown exerted tumor-suppressive functions. We observed that PVT1 promotes malignant cell behavior by decreasing miR-195-5p expression. Binding of PVT1 and miR-195-5p was confirmed using luciferase assays. Furthermore, expression of miR-195-5p negatively correlates with PVT1 expression. At the molecular level, either PVT1 knockdown or miR-195-5p overexpression resulted in a decrease of acidic fibroblast growth factor receptor (FGFR1)44FGFR1: acidic fibroblast growth factor receptor. and basic fibroblast growth factor (FGF2).55FGF2: basic fibroblast growth factor. FGFR1 and FGF2 are targets of miR-195-5p that play a critical role in endometrial carcinoma by activating PI3K/AKT and MAPK/Erk pathways. Remarkably, PVT1 knockdown combined with miR-195-5p overexpression led to tumor regression in vivo. Overall, these results depict a novel pathway mediated by PVT1 in endometrial carcinoma, which may have potential application for endometrial carcinoma therapy.

RETRACTED ARTICLE: LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis

BackgroundDefective autophagy is thought to contribute to the pathogenesis of many diseases, including cancer. Human plasmacytoma variant translocation 1 (PVT1) is an oncogenic long non-coding RNA that has been identified as a prognostic biomarker in pancreatic ductal adenocarcinoma, but how PVT1 operates in the regulation of autophagy in pancreatic ductal adenocarcinoma (PDA) is unclear.MethodsPVT1 expression level was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and hybridization in situ (ISH). Western blot or qRT-PCR was performed to assess the ULK1 protein or mRNA level. Autophagy was explored via autophagic flux detection under a confocal microscope and autophagic vacuoles investigation under a transmission electron microscopy (TEM). The biological role of PVT1 in autophagy and PDA development was determined by gain-of-function and loss-of-function assays.ResultsWe found that PVT1 levels paralleled those of ULK1 protein in PDA cancer tissues. PVT1 promoted cyto-protective autophagy and cell growth by targeting ULK1 both in vitro and in vivo. Moreover, high PVT1 expression was associated with poor prognosis. Furthermore, we found that PVT1 acted as sponge to regulate miR-20a-5p and thus affected ULK1 expression and the development of pancreatic ductal adenocarcinoma.ConclusionsThe present study demonstrates that the “PVT1/miR-20a-5p/ULK1/autophagy” pathway modulates the development of pancreatic ductal adenocarcinoma and may be a novel target for developing therapeutic strategies for pancreatic ductal adenocarcinoma.

Long non-coding RNA PVT1 promotes cell proliferation and invasion through regulating miR-133a in ovarian cancer

The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), was reportedly to be highly expressed in a variety of tumors including ovarian cancer (OC). However, the role and mechanism of action of PVT1 in the carcinogenesis and progression of OC remains largely unknown. PVT1 and miR-133a expression were detected by quantitative real time PCR(qRT-PCR) assays in OC tissues and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometer, wound healing and transwell invasion assays were performed to evaluate cell proliferation, cycle, migration and invasion abilities, respectively. qRT-PCR and luciferase reporter assays demonstrated PVT1 regulated miR-133a expression. Here, we discovered that PVT1 shows higher expression in OC tissues than in normal ovarian tissues, and patients who show higher expression of PVT1 have worse progression-free and overall survivals compared to lower expression of PVT1. Additionally, we observed that knockdown of PVT1 significantly inhibited OC cell proliferation, and decreased the migration and invasion capabilities of OC cells. Mechanistically, miR-133a was identified to serve as a direct downstream target of PVT1 in OC. Knockdown of PVT1 inhibited cell proliferation, migration and invasion through negative regulating miR-133a in OC cells. Taken together, our finding shows that PVT1 may be a novel biomarker for prognosis and a promising therapeutic target for OC.

Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer.

Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues (P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.

Knockdown of long non‑coding RNA PVT1 reverses multidrug resistance in colorectal cancer cells.

Multidrug resistance (MDR) is one of the primary causes of chemotherapy failure in colorectal cancer (CRC), and extensive biological studies into MDR are required. The non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been demonstrated to be associated with low survival rates in patients with CRC. However, whether PVT1 serves a critical function in the MDR of CRC remains to be determined. To determine the association between PVT1 expression and 5-fluorouracil (5-FU) resistance in CRC, the expression levels of PVT1 mRNA in 5-FU-resistant CRC tissues and cell lines (HCT-8/5-FU and HCT-116/5-FU) were assessed by a reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cytotoxicity was evaluated using a Cell Counting Kit-8 assay and apoptosis rates were assessed via flow cytometry. In the present study, PVT1 mRNA was highly expressed in 5-FU-resistant CRC tissues and cell lines. HCT-8/5-FU and HCT-116/5-FU cells transfected with small interfering RNA PVT1 and treated with 5-FU exhibited higher apoptotic rates and lower survival rates. By contrast, overexpression of PVT1 in HCT-8 and HCT-116 cells transfected with lentiviral vector-PVT1-green fluorescent protein and treated with 5-FU exhibited lower apoptosis rates and higher survival rates. RT-qPCR and western blotting demonstrated that the overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistance-associated protein 1, P-glycoprotein, serine/threonine-protein kinase mTOR and apoptosis regulator Bcl2. The present study indicates that PVT1 overexpression may promote MDR in CRC cells, and suggested that inhibition of PVT1 expression may be an effective therapeutic strategy for reversing MDR in CRC.

Upregulated plasmacytoma variant translocation 1 promotes cell proliferation, invasion and metastasis in colorectal cancer.

Emerging evidence indicates that the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is associated with tumourigenesis in various types of cancer. However, its specific effects on the proliferation, invasion and metastasis of colorectal cancer (CRC) are still poorly understood. The present study aimed to investigate PVT1 expression in CRC and explore its role in CRC pathogenesis. The reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) technique was used to assess PVT1 expression in CRC cell lines. Gene Expression Omnibus (GEO) database analysis and measurement of clinical samples was used to analyse the correlation between PVT1 expression, CRC metastasis and overall survival (OS). In addition, knockdown of PVT1 expression was performed using short interfering RNA (siRNA) and RT-qPCR, western blotting, CCK-8 assays, tumour cell clone-formation and Matrigel invasion assays were used to observe its biological functions in HCT116 cells. The present study demonstrated that the expression of PVT1 in CRC cell lines was higher than that in normal colon mucosal cell lines. Using GEO database analysis and the measurement of clinical samples, it was revealed that CRC patients with high PVT1 expression demonstrated poor OS. Multivariate analysis indicated that high PVT1 expression is an independent risk factor for patients with CRC. In addition, PVT1 knockdown suppressed the proliferation, invasion and metastasis of CRC cells in vitro, which were associated with decreasing vimentin, cyclin D1 and cyclin-dependent kinase 4 expression and enhanced E-cadherin expression. The results of the present study suggest that PVT1 may serve a critical role in CRC progression and metastasis and may serve as a potential prognostic biomarker for CRC.

Long non-coding RNA PVT1 predicts poor prognosis and induces radioresistance by regulating DNA repair and cell apoptosis in nasopharyngeal carcinoma

The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), is highly expressed in a variety of tumors, and is believed to be a potential oncogene. However, the role and mechanism of action of PVT1 in the carcinogenesis and progression of nasopharyngeal carcinomas (NPCs) remains unclear. In this study, for the first time, we have discovered that PVT1 shows higher expression in NPCs than in normal nasopharyngeal epithelial tissue, and patients with NPCs who show higher expression of PVT1 have worse progression-free and overall survivals. Additionally, we observed that the proliferation of NPC cells decreased, and their rate of apoptosis increased; these results indicated that the knockdown of PVT1 expression in the NPC cells induced radiosensitivity. Further, we have shown that the knockdown of PVT1 expression can induce apoptosis in the NPC cells by influencing the DNA damage repair pathway after radiotherapy. In general, our study shows that PVT1 may be a novel biomarker for prognosis and a new target for the treatment of NPCs. Additionally, targeting PVT1 may be a potential strategy for the clinical management of NPC and for the improvement of the curative effect of radiation in NPCs.

Long non-coding RNA PVT1 facilitates cell proliferation by epigenetically regulating FOXF1 in breast cancer.

Background: plasmacytoma variant translocation 1 (PVT1) has been identified as an oncogenic long non-coding RNA (lncRNA) in multiple cancers including breast cancer. However, its molecular basis has not been exhaustively elucidated. Methods: RT-qPCR assay was used to detect PVT1 expression in tissues and cells. The effect of PVT1 and FOXF1 on breast cancer cell proliferation was assessed by MTT, colony formation and cell cycle assays. Cell apoptotic rate was measured by flow cytometry via double-staining of Annexin V-FITC and PI. The protein expression patterns of forkhead box f1 (FOXF1) and enhancer of zeste homolog 2 (EZH2) were detected using western blot assays. The subcellular location of PVT1 was analyzed using subcellular fractionation assays. The interaction between PVT1 and EZH2 were demonstrated by RNA-protein pull down and RIP assays. ChIP assay was used to explore whether PVT1 affected FOXF1 expression by recruiting EZH2. In vivo assays were performed to further investigate the roles of PVT1 in breast cancer tumorigenesis. Results: PVT1 expression was elevated in breast cancer tissues and cells. Moreover, higher PVT1 level was positively associated with aggressive pathological status and poor prognosis of breast cancer. PVT1 knockdown suppressed proliferation and induced apoptosis in breast cancer cells. PVT1 silenced FOXF1 expression by recruiting EZH2 to the promoter region of FOXF1, resulting in the increase of H3K27me3 level. EZH2 inhibitor EPZ005687 counteracted PVT1-mediated enrichment effect on H3K27me3 and EZH2 to FOXF1 promoter region. FOXF1 overexpression hampered proliferation and facilitated apoptosis in breast cancer cells. Furthermore, down-regulation of FOXF1 partly abrogated PVT1-knockdown-mediated anti-proliferation and pro-apoptosis effect in breast cancer cells. Finally, PVT1 deficiency suppressed tumor growth by promoting FOXF1 expression in vivo. Conclusion: PVT1 promoted cell proliferation and suppressed apoptosis by epigenetically silencing FOXF1 expression through EZH2 in breast cancer.

Long non-coding RNA PVT1 indicates a poor prognosis of glioma and promotes cell proliferation and invasion via target EZH2

Human glioma is one of the malignant tumors of the central nervous system (CNS). Its prognosis is poor, which is due to its genetic heterogeneity and our poor understanding of its underlying molecular mechanisms. The present study aimed to assess the relationship between plasmacytoma variant translocation 1 (PVT1) and enhancer of zeste homolog 2 (EZH2), and their effects on the proliferation and invasion of glioma cells. The expression levels of PVT1 and EZH2 in human glioma tissues and cell lines were measured using quantitative RT-PCR (qRT-PCR). Then, after siRNA-PVT1 and entire PVT1 sequence vector transfection, we determined the regulation roles of PVT1 in the proliferation, apoptosis, migration, and invasion of glioma cells. We found that the expression levels of both PVT1 and EZH2 were up-regulated in human glioma tissues and cell lines, and positively correlated with glioma malignancy. And, silencing of PVT1 expression resulted in decreased proliferation, increased apoptosis, and decreased migration and invasion. In addition, exogenous PVT1 led to increased EZH2 expression and increased proliferation and induced proliferation and invasion. These data inferred that long non-coding RNA PVT1 could be served as an indicator of glioma prognosis, and PVT1–EZH2 regulatory pathway may be a novel therapeutic target for treating glioma.

LncRNA PVT1 predicts prognosis and regulates tumor growth in prostate cancer.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1(PVT1) was aberrantly expressed in various cancers and is associated with tumor prognosis. Here, we aim to investigate its function in prostate cancer. Small interfering RNA against PVT1 was transfected into prostate cancer cell lines and cell growth and apoptosis were analyzed. Our results showed that PVT1 was overexpressed in prostate cancer tissues and cells. Higher levels of PVT1 indicated poorer overall survival and disease-free survival. A significant association was found between PVT1 expression and tumor stage. Besides, PVT1 knockdown significantly inhibited prostate cancer growth in vivo and in vitro and promoted cell apoptosis. PVT1 knockdown also significantly upregulated the expression of cleaved caspase-3 and cleaved caspase-9, but downregulated the expression of c-Myc in prostate cancer cell lines. Our results suggest that PVT1 played an oncogenic role in prostate cancer and could be used as a potential biomarker for diagnosis of prostate cancer.

Prognostic value of long non-coding RNA PVT1 as a novel biomarker in various cancers: a meta-analysis.

BackgroundPlasmacytoma variant translocation 1 (PVT1) has recently been reported to be aberrantly expressed and serves as a prognostic biomarker in many types of cancers. However, its prognostic significance remains controversial. Here, we conducted a meta-analysis to investigate the prognostic value of PVT1 expression in cancers.ResultsA total of 2109 patients from 20 studies were included. The results showed that elevated PVT1 expression predicted a poor outcome for overall survival (OS) in nine types of cancers (HR = 1.40, 95% CI: 1.21–1.59). Subgroup analysis indicated that there was a significant association between PVT1 overexpression and poor OS of patients with gastric cancer, gynecology cancer and lung cancer. Furthermore, we also found a negative significant relationship between PVT1 expression and disease-free survival (HR = 1.83, 95% CI: 1.39–2.27), progression-free survival (HR = 1.63, 95% CI: 1.34–1.93) and recurrence-free survival (HR = 1.74, 95% CI: 1.01–2.47). In addition, the level of PVT1 expression was positively related to tumor size, TNM stage, lymph node metastasis and distant metastases.Materials and MethodsA systematic search was performed through the PubMed, EMBASE, Web of Science, Ovid and Cochrane library databases for eligible studies on prognostic value of PVT1 in cancers from inception up to June, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association between PVT1 expression and clinical outcomes.ConclusionsPVT1 expression positively related to tumor size, TNM stages, lymph node metastasis and distant metastases, and served as a prognostic biomarker in different types of cancers.

Knockdown of LncRNA PVT1 inhibits tumorigenesis in non-small-cell lung cancer by regulating miR-497 expression

Plasmacytoma variant translocation1 (PVT1) was reported to be upregulated in non-small-cell lung cancer (NSCLC) tissues, serve as a promising biomarker for diagnosis and prognosis of NSCLC, and promoted NSCLC cell proliferation. However, the detailed molecular mechanism of PVT1 involved in the pathogenesis and development of NSCLC remains largely unknown. In this study, the expression levels of PVT1 and miR-497 in NSCLC cells were determined by qRT-PCR. Cell viability, invasion and apoptosis were detected by MTT assay, cell invasion assay and flow cytometry analysis, respectively. RNA immunoprecipitation (RIP) and luciferase reporter assay were performed to confirm whether PVT1 directly interacts with miR-497. A xenograft mouse model was established to confirm the effect of PVT1 on tumor growth in vivo and the underlying molecular mechanism. Our findings indicated that PVT1 was significantly upregulated and miR-497 was markedly downregulated in NSCLC cell lines. si-PVT1 effectively decreased the expression of PVT1 and increased the expression of miR-497. PVT1 knockdown remarkably inhibited cell viability, invasion and promoted apoptosis in NSCLC cells. RIP and luciferase reporter assay demonstrated that PVT1 could directly interact with miR-497. Moreover, PVT1 overexpression reversed the inhibitory effect of miR-497 on cell viability, invasion and promotion effect on apoptosis of NSCLC cells. Furthermore, in vivo experiment showed that knockdown of PVT1 inhibited tumor growth in vivo and promoted miR-497 expression. In conclusion, knockdown of PVT1 inhibited cell viability, invasion and induced apoptosis in NSCLC by regulating miR-497 expression, elucidating the molecular mechanism of the oncogenic role of PVT1 in NSCLC and providing an lncRNA-directed target for NSCLC.

Long non‐coding RNA PVT1: Emerging biomarker in digestive system cancer

The digestive system cancers are leading cause of cancer-related death worldwide, and have high risks of morbidity and mortality. More and more long non-coding RNAs (lncRNAs) have been studied to be abnormally expressed in cancers and play a key role in the process of digestive system tumour progression. Plasmacytoma variant translocation 1 (PVT1) seems fairly novel. Since 1984, PVT1 was identified to be an activator of MYC in mice. Its role in human tumour initiation and progression has long been a subject of interest. The expression of PVT1 is elevated in digestive system cancers and correlates with poor prognosis. In this review, we illustrate the various functions of PVT1 during the different stages in the complex process of digestive system tumours (including oesophageal cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma and pancreatic cancer). The growing evidence shows the involvement of PVT1 in both proliferation and differentiation process in addition to its involvement in epithelial to mesenchymal transition (EMT). These findings lead us to conclude that PVT1 promotes proliferation, survival, invasion, metastasis and drug resistance in digestive system cancer cells. We will also discuss PVT1's potential in diagnosis and treatment target of digestive system cancer. There was a great probability PVT1 could be a novel biomarker in screening tumours, prognosis biomarkers and future targeted therapy to improve the survival rate in cancer patients.

Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1.

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased cleaved caspase-3 and cleaved PARP. PVT1 increased Mcl-1 mRNA levels in renal cancer cells by promoting mRNA stability without influencing its transcription. in vitro, the enhanced apoptosis arising from PVT1 suppression was attenuated by overexpressing Mcl-1. In addition, in vivo experiments showed that PVT1 knockdown repressed xenograft tumor growth, while Mcl-1 overexpression partially rescued xenograft tumor growth. These results indicate the PVT1/Mcl-1 pathway inhibits renal cancer cell apoptosis in vitro and in vivo. PVT1 may thus serve as a novel biomarker, and the PVT1/Mcl-1 pathway may be a useful therapeutic target for clear cell renal cell carcinoma.

Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS) with multiple genetic and environmental risk factors. Long non-coding RNAs (lncRNAs) have been recently reported to participate in the regulation of immune responses. Consequently, aberrant expression of lncRNAs has been suggested as an underlying cause of MS. In the present study, we evaluated the expression of three lncRNAs with putative roles in the regulation of immune response, namely TNF-α and heterogeneous nuclear ribonucleoprotein L (THRIL), Fas cell surface death receptor- antisense 1 (FAS-AS1), and plasmacytoma variant translocation 1 (PVT1) in circulating blood cells of 50 Iranian relapsing-remitting multiple sclerosis (RRMS) patients compared with healthy subjects by means of quantitative real-time polymerase chain reaction (PCR). We detected a significant downregulation of PVT1 and FAS-AS1 expressions in RRMS patients while a significant upregulation of THRIL in patients compared with controls (P<0.001). Correlation analyses between lncRNA expression levels and clinical data of MS patients revealed no significant correlation between lncRNAs expression levels and Expanded Disability Status Scale (EDSS), a moderate correlation between PVT1 expression levels and duration of the disorder and no significant correlation between lncRNAs expression levels and age at onset. In addition, we demonstrated correlations between the expression levels of PVT1 and THRIL as well as expression levels of THRIL and FAS-AS1 in RRMS patients. In brief, we have demonstrated dysregulation of three lncRNAs in MS patients. Further studies are needed to explore the exact mechanisms by which these lncRNAs participate in regulation of immune responses.

Long Noncoding RNA PVT1 Facilitates Cervical Cancer Progression via Negative Regulating of miR-424.

Emerging evidence suggests that the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) gene is involved in the pathogenesis of cervical cancer. However, the potential mechanism is rarely reported. Our study found that PVT1 was upregulated in cervical cancer tissue and cell lines. After transfecting PVT1 siRNA, the proliferation, migration, and invasion of cervical cancer cells were markedly decreased. miRNA expression profiles demonstrate that miR-424 was markedly downregulated in cervical cancer tissue. Bioinformatics analysis revealed that miR-424 was potentially targeted by PVT1, which was confirmed by dual-luciferase reporter assay. Pearson’s correlation analysis showed that PVT1 expression was negatively related to miR-424 expression in glioma cancer tissues. Finally, lowered expression of miR-424 could recover the tumor-suppressive effects of PVT1 knockdown in cervical cancer cell lines. Our results reveal a tumor-promoting role for PVT1, acting as a competing endogenous RNA (ceRNA) or a molecular sponge in negatively modulating miR-424, which might provide a novel therapeutic target for cervical cancer.

LncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression

Long non-coding RNAs (lncRNAs) exert critical regulatory roles in the development and progression of several cancers. Plasmacytoma variant translocation 1 (PVT1), an lncRNA, was shown to be upregulated in clear cell renal cell carcinoma (ccRCC) in our study, while Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival (OS) and disease free survival (DFS) in ccRCC patients. In vitro experiments revealed that PVT1 promoted renal cancer cell proliferation, migration, and invasion, while in vivo studies confirmed its oncogenic roles in ccRCC. Further bioinformatic analysis and RNA immunoprecipitation revealed that PVT1 could function as an oncogenic transcript partly through sponging miR-200s to regulate BMI1, ZEB1 and ZEB2 expression. Besides, a novel splicing variant of PVT1 lacking exon 4 (PVT1ΔE4) was found to have a higher expression in ccRCC and could also promote cell proliferation and invasion as the full-length transcript did. Besides, SRSF1 decreased the inclusion of exon 4 of full-length transcript and increased the relative expression of PVT1ΔE4 in ccRCC. Mechanistic investigations indicated that PVT1ΔE4 could also upregulate the expression of BMI1, ZEB1 and ZEB2 through interacting with miR-200s. Our study helps reveal new molecular events in ccRCC and provides promising diagnostic and therapeutic targets for this disease.

LncRNA plasmacytoma variant translocation 1 is an oncogene in bladder urothelial carcinoma.

Bladder cancer (BC) is the most lethal malignant cancer of the genitourinary system, and bladder urothelial carcinoma (BUC) is the most common type of BC. The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is overexpressed in several malignant tumors, including BC. Using a lncRNA array and quantitative real-time PCR, we detected greater expression of PVT1 in BUC tissues and cell lines resistant to doxorubicin (DOX) and cisplatin (DDP) than in DOX- and DDP-sensitive cells. PVT1 knockdown reduced proliferation and invasion by a DOX- and DDP-resistant T24/DR BUC cells, arrested cells in G1 phase, and increased apoptosis. PVT1 knockdown also sensitized T24/DR cells to DOX and DDP, and suppressed expression of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1). Wnt/β-catenin pathway activation in T24/DR cells reversed the effects of PVT1 knockdown on metastasis-associated behavior and chemoresistance. In sum, lncRNA PVT1 is overexpressed in multidrug resistant BUC tissues and cell lines, and PVT1 knockdown reduces BUC cell proliferation, invasiveness, and chemoresistance by modulating Wnt/β-catenin signaling. These results provide new insight into BUC chemoresistance mechanisms and suggest potential therapeutic targets for anti-BUC therapeutics.

LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a Sponge for miR-488-3p.

Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse diseases, including osteoarthritis (OA). The present study aims at exploring the biological role of lncRNA plasmacytoma variant translocation 1 (PVT1) in OA and the underlying mechanism. Results showed that the expression of PVT1 was upregulated in OA chondrocytes compared with normal chondrocytes, silencing PVT1 inhibited the apoptosis of OA chondrocytes, and overexpression of PVT1 promoted the apoptosis of normal chondrocytes. To further investigate the underlying mechanism, miR-488-3p was predicted to be a targeted microRNA of PVT1. Different methods, including MS2 RNA immunoprecipitation (RIP), luciferase activity, and anti-AGO2 RIP, were performed to detect the interaction between PVT1 and miR-488-3p, which suggested that PVT1 negatively regulated miR-488-3p in OA chondrocytes. Moreover, PVT1 promoted the apoptosis of OA and normal chondrocytes through miR-488-3p. Collectively, this study revealed that lncRNA PVT1 regulated the apoptosis of chondrocytes by acting as a sponge for miR-488-3p in OA. PVT1 may be considered a new therapeutic target for the treatment of OA.