LncRNA-PVT1 Inhibits Ferroptosis through Activating STAT3/GPX4 Axis to Promote Osteosarcoma Progression.

BACKGROUND: Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis. METHODS: The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB). RESULTS: PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated. CONCLUSION: PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.

M1 Macrophage-Derived Exosome LncRNA PVT1 Promotes Inflammation and Pyroptosis of Vascular Smooth Muscle Cells in Abdominal Aortic Aneurysm by Inhibiting miR-186-5p and Regulating HMGB1.

Abdominal aortic aneurysm (AAA) is a chronic vascular degenerative disease. Vascular smooth muscle cells (VSMCs) are essential for maintaining the integrity of healthy blood vessels. Macrophages play an important role in the inflammatory process of AAA. However, the effect of macrophage-derived exosome LncRNA PVT1 on VSMCs is unclear. Exosomes from M1 macrophages (M1φ-exos) were isolated and identified. The expression of LncRNA PVT1 in M1φ-exos was determined. AAA cell model was constructed by treating VSMCs with Ang-II. AAA cell model was treated with M1φ exosomes transfected with si-LncRNA PVT1 (M1φsi-LncRNA PVT1-exo). VSMCs were transfected with miR-186-5p mimic and oe-HMGB1. Cell viability was detected by CCK-8. The accumulation of LDH was detected by ELISA. Western blot was used to detect the expression of HMGB1, inflammatory factors (IL-6, TNF-α and IL-1ß) and pyroptosis-related proteins (GSDMD, N-GSDMD, ASC, NLRP3, Caspase-1 and Cleaved-Capase-1). Cell pyroptosis rate was detected by flow cytometry. At the same time, the targeting relationship between miR-186-5p and LncRNA PVT1 and HMGB1 was verified by double fluorescein experiment. Exosomes from M1φ were successfully extracted. The expression of LncRNA PVT1 in M1φ-exos was significantly increased. M1φ-exo promotes inflammation and pyroptosis of VSMCs. M1φsi-LncRNA PVT1-exos inhibited the inflammation and pyroptosis of VSMCs. LncRNA PVT1 can sponge miR-186-5p mimic to regulate HMGB1 expression. MiR-186-5p mimic further inhibited inflammation and pyroptosis induced by M1φsi-LncRNA PVT1-exos. However, oe-HMGB1 could inhibit the reversal effect of miR-186-5p mimic. LncRNA PVT1 in exosomes secreted by M1φ can regulate HMGB1 by acting as ceRNA on sponge miR-186-5p, thereby promoting cell inflammatory and pyroptosis and accelerating AAA progression.

PVT1 lncRNA in lung cancer: A key player in tumorigenesis and therapeutic opportunities.

The lncRNA PVT1 has emerged as a pivotal component in the intricate landscape of cancer pathogenesis, particularly in lung cancer. PVT1, situated in the 8q24 chromosomal region, has garnered attention for its aberrant expression patterns in lung cancer, correlating with tumor progression, metastasis, and poor prognosis. Numerous studies have unveiled the diverse mechanisms PVT1 contributes to lung cancer pathogenesis. It modulates critical pathways, such as cell proliferation, apoptosis evasion, angiogenesis, and epithelial-mesenchymal transition. PVT1's interactions with other molecules, including microRNAs and proteins, amplify its oncogenic influence. Recent advancements in genomic and epigenetic analyses have also illuminated the intricate regulatory networks that govern PVT1 expression. Understanding PVT1's complex involvement in lung cancer holds substantial clinical implications. Targeting PVT1 presents a promising avenue for developing novel diagnostic biomarkers and therapeutic interventions. This abstract encapsulates the expanding knowledge regarding the oncogenic role of PVT1 in lung cancer, underscoring the significance of further research to unravel its complete mechanistic landscape and exploit its potential for improved patient outcomes.

LncRNA PVT1: as a therapeutic target for breast cancer.

A significant number of women are identified with breast cancer (BC) every year, making it among the most prevalent malignancies and one of the leading causes of mortality globally. Despite significant progress in understanding BC pathogenesis and treatment options, there is still a need to identify new therapeutic targets and develop more effective treatments. LncRNAs have been discovered as biomarkers and a promising target for various cancers, including BC. PVT1 is a particular one of these lncRNAs, and research has indicated that it has a significant impact on the appearance and progression of BC.PVT1 is an attractive therapeutic target for BC due to its role in promoting cancer cell growth, metastasis and invasion. In addition to its potential as a treatment strategy, PVT1 may also have diagnostic value in BC. In this article, we will discuss targeting PVT1 as a treatment strategy for BC.

LncRNA PVT1 promotes bladder cancer progression by forming a positive feedback loop with STAT5B.

BACKGROUND: Plasmacytoma Variant Translocation 1 (LncRNA PVT1) and signal transducer and activator of transcription 5B (STAT5B) play important roles in various cancers, but their interaction in bladder cancer (BC) remains unclear. PURPOSE: We aimed to explore the interaction between lncRNA PVT1 and STAT5B in BC tumorigenesis and find potential drugs for BC. METHODS: The association of the expression of lncRNA PVT1 and STAT5B to the prognosis of BC patients was evaluated via bioinformatic analysis. Loss- and gain-of-function assays were performed to determine the biological functions of lncRNA PVT1 and STAT5B. Quantitative real time polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence were used to detect lncRNA PVT1 and STAT5B expression. Fluorescence in situ hybridization, RNA pull-down and RNA immunoprecipitation assays were conducted to determine the regulatory effect of lncRNA PVT1 on STAT5B. The transcriptional effect of STAT5B on lncRNA PVT1 gene was determined using luciferase reporter assay, chromatin immunoprecipitation and DNA-affinity precipitation assays. Connectivity Map analysis was used to screen anticancer drugs. RESULTS: LncRNA PVT1 and STAT5B enhance the expression of each other and promote the malignant phenotypes in BC, including cell viability and invasion. lncRNA PVT1 stabilizes STAT5B by decreasing ubiquitination, enhances STAT5B phosphorylation, and promotes the translocation to the nucleus of STAT5B to trigger further carcinogenesis activities. In the nucleus, STAT5B activates the transcription of lncRNA PVT1 by binding directly to its promoter region, leading to a positive feedback. Tanespimycin effectively abated the oncogenic effect. CONCLUSIONS: We first identified the lncRNA PVT1/STAT5B positive feedback loop for bladder carcinogenesis, and found a potentially effective drug for BC.

LncRNA PVT1 inhibits endothelial cells apoptosis in coronary heart disease through regulating MAPK1 expression via miR-532-3p.

Background: Coronary atherosclerotic heart disease (CAD) is an inflammatory vascular disease caused by atherosclerosis. Long non-coding RNAs are involved in the pathophysiological process of coronary heart disease. Here we investigated the regulatory effects of lncRNA PVT1 (PVT1) in human coronary artery endothelial cells (HCAECs).Methods: qRT-PCR and western blot were performed to detect gene and protein expressions. CCK-8, flow cytometry and wound healing assays were used to determine cell viability, apoptosis and migration of HCAECs. The binding relationship among miR-532-3p, PVT1 and MAPK1 was verified by dual luciferase reporter assay.Results: Overexpression of PVT1 markedly reduced cell apoptosis and increased cell proliferation and migration. However, miR-532-3p upregulation suppressed cell proliferation and migration and promoted apoptosis of HCAECs. PVT1 suppressed the expression of miR-532-3p via directly targeting miR-532-3p. And miR-532-3p overexpression abolished the effect of PVT1 upregulation on proliferation and apoptosis in HCAECs. Furthermore, MAPK1 acted as a target gene of miR-532-3p and miR-532-3p inhibited MAPK1 expression.Conclusion: PVT1 promoted MAPK1 expression by targeting miR-532-3p, thus inhibiting HCAECs apoptosis and promoting cell proliferation, suggesting PVT1 might have great potential as a therapeutic target for CAD.

Identification of hub necroptosis-related lncRNAs for prognosis prediction of esophageal carcinoma.

Necroptosis is a newly identified programmed cell death associated with the biological process of various cancers, including esophageal carcinoma (ESCA). Meanwhile, the dysregulation of long non-coding RNAs (lncRNAs) is greatly implicated in ESCA progression and necroptosis regulation. However, the lncRNAs involved in regulating necroptosis in ESCA are still unclear. In this study, we aim to explore the expression profile of necroptosis-related lncRNAs (NRLs), and evaluate their roles in ESCA prognosis and treatment. In the present study, 198 differentially expressed NRLs were identified between the ESCA and adjacent normal tissues through screening the data extracted from the Cancer Genome Atlas (TCGA) database. And, a prognostic panel consisting of 6 NRLs was constructed using the LASSO algorithm and multivariate Cox regression analysis. The ESCA patients with high risks had a markedly reduced survival time and higher mortality prevalence. Moreover, C-index of 6 NRLs-panel was superior to 48 published prognostic models based on lncRNAs or mRNAs for ESCA. There were significant differences between the high-risk and low-risk groups in tumor-related pathways, genetic mutations, and drug sensitivity responses. In vitro analysis revealed that inhibition of PVT1 impeded the proliferation, migration, and colony formation of ESCA cells, increased the expressions of p-RIP1 and p-MLKL and promoted necroptosis. By contrast, PVT1 overexpression resulted in a decrease in necroptotic cell death events, thus promoting tumor progression. Collectively, the established 6-NRLs panel was a promising biomarker for the prognostic prediction of ESCA. Moreover, our current findings provided potential targets for individualized therapy for ESCA patients.

Long non-coding RNA PVT1 regulates atherosclerosis progression via the microRNA-106b-5p/ACSL4 axis.

Long non-coding RNAs (lncRNAs) have been associated with atherosclerosis (AS), but the role of lncRNA PVT1 in this disease is still unknown. However, lncRNA PVT1 was found to be significantly upregulated in the serum of AS patients. In vitro experiments using human vascular endothelial cells (HUVECs) showed that oxidized low-density lipoprotein (ox-LDL) treatment enhanced PVT1 expression and impeded HUVEC proliferation, which could be reversed by PVT1 knockdown or miR-106b-5p mimics. Additionally, knockdown of PVT1 and overexpression of miR-106b-5p inhibited the increase of iron content, MDA level, lipid ROS, ACSL4, and PTGS2 in ox-LDL-induced HUVECs, as well as the decrease of GSH and GPX4. We also found that PVT1 knockdown reduced lipid deposition, atherosclerotic plaque number, and size in ApoE-/- mice. These results suggest that PVT1 plays a crucial role in AS progression by regulating the miR-106b-5p/ACSL4 axis in HUVECs, and may therefore be a potential therapeutic target for AS.

LncRNA PVT1 influences breast cancer cells glycolysis through sponging miR-145-5p.

BACKGROUND: Long-non-coding RNA PVT1 (lncRNA PVT1) can be used as an oncogenic regulatory non-coding RNA (ncRNA) for many cancers. However, its function and mechanism in breast cancer (BRCA) are still not clearly elucidated. OBJECTIVE: We attempt to explain the mechanism of PVT1's role in breast cancer from different perspectives. METHODS: We analyzed the expression of PVT1 and its correlation with the breast cancer related clinical data in the The Cancer Genome Atlas (TCGA) database. We used PVT1 overexpression and knockdown lentivirus to infect breast cancer MDA-MB-231 cell line for cell function verification, in vitro using CCK-8 to measure proliferation, flow cytometry to measure apoptosis, transwell test to measure invasion and migration ability, detecting cell extracellular acidification rate (ECAR) to assess glycolysis metabolism and explore the biological functions of PVT1 in breast cancer cells. Transcriptome sequencing was used to analyze the changes of related genes in cells after overexpression of PVT1. In vivo we used a xenograft model to study the effect of PVT1 on breast cancer. RESULTS: PVT1 was up-regulated in breast cancer tissues and was positively correlated with the clinical stage of breast cancer patients. Overexpression of PVT1 in vitro promoted cell proliferation, migration and invasion, and promoted tumor growth in vivo. Knockdown of PVT1 led to the opposite biological consequence. Further bioinformatics analysis showed that PVT1 changes the glycolysis metabolism of tumors through regulation of glycolysis-related genes. In addition, the expression of miR-145-5p is negatively correlated with PVT1. We consider the possibility of PVT1 promoting cell proliferation and metastasis by regulating the aerobic glucose metabolism in breast cancer cells through sponging the miR-145-5p. CONCLUSION: Our results reveal a potential pathway for competing endogenous RNA to regulate breast cancer glucose metabolism. PVT1 regulates glycolysis related genes expression by competitively binding to endogenous miR-145-5p in breast cancer cells to change the metabolic phenotype. This may Provide new ideas for precise molecular therapy targets for breast cancer.

LncRNA PVT1 delays skin photoaging by sequestering miR-551b-3p to release AQP3 expression via ceRNA mechanism.

Understanding human skin photoaging requires in-depth knowledge of the molecular and functional mechanisms. Human dermal fibroblasts (HDFs) gradually lose their ability to produce collagen and renew intercellular matrix with aging. Therefore, our study aims to reveal the mechanistic actions of a novel ceRNA network in the skin photoaging by regulating HDF activities. Photoaging-related genes were obtained in silico, followed by GO and KEGG enrichment analyses. Differentially expressed lncRNAs and miRNAs were screened from the GEO database to construct the ceRNA co-expression network. In skin photoaging samples, PVT1 and AQP3 were poorly expressed, while miR-551b-3p was highly expressed. The relationships among the lncRNA, miRNA and mRNA were explored through the ENCORI database and dual luciferase reporter assay. Mechanistically, PVT1 could sequester miR-551b-3p to upregulate the expression of AQP3, which further inactivated the ERK/p38 MAPK signaling pathway. HDFs were selected to construct an in vitro cell skin photoaging model, where the senescence, cell cycle distribution and viability of young and senescent HDFs were detected by SA-ß-gal staining, flow cytometry and CCK-8 assay. In vitro cell experiments confirmed that overexpression of PVT1 or AQP3 enhanced viability of young and senescent HDFs and inhibited HDF senescence, while miR-551b-3p upregulation counteracted the effect of PVT1. In conclusion, PVT1-driven suppression of miR-551b-3p induces AQP3 expression to inactivate the ERK/p38 MAPK signaling pathway, thereby inhibiting HDF senescence and ultimately delaying the skin photoaging.

LncRNA PVT1 Promotes Neuronal Cell Apoptosis and Neuroinflammation by Regulating miR-488-3p/FOXD3/SCN2A Axis in Epilepsy.

It is vital to understand the mechanism of epilepsy onset and development. Dysregulated lncRNAs are closely associated with epilepsy. Our work probed the role of lncRNA PVT1/miR-488-3p/FOXD3/SCN2A axis in epilepsy. The mRNA and protein expressions were assessed using qRT-PCR and western blot. MTT assay and TUNEL staining were conducted to assess cell viability and apoptosis, respectively. TNFα, IL-1ß and IL-6 levels were analyzed using ELISA. LDH level was tested by Assay Kit. The binding relationship between PVT1, miR-488-3p and FOXD3 were verified using dual luciferase reporter gene assay. The epilepsy model of rats was established by lithium-pilocarpine injection. Nissl staining was performed to evaluate neuronal damage. PVT1 was markedly upregulated in epilepsy model cells. Knockdown of PVT1 increased the viability, while repressed the apoptosis and inflammatory cytokines secretion as well as LDH level in epilepsy cell model. MiR-488-3p alleviated neuronal injury and neuroinflammation in model cells. MiR-488-3p functioned as the direct target of PVT1, and its inhibition neutralized the effects of PVT1 silencing on neuronal cell injury and neuroinflammation in model cells. Furthermore, miR-488-3p inhibited neuronal cell injury and neuroinflammation in model cells by regulating FOXD3/SCN2A pathway. Finally, animal experiments proved that PVT1 promoted epilepsy-induced neuronal cell injury and neuroinflammation by regulating miR-488-3p-mediated FOXD3/SCN2A pathway. PVT1 promoted neuronal cell injury and inflammatory response in epilepsy via inhibiting miR-488-3p and further regulating FOXD3/SCN2A pathway.

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-ß1) 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-ß1 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 Regulates miR-1207-5p to Affect Colon Cancer Proliferation and Migration via the Wnt6/ß-catenin2 Pathway.

Background: We aimed to evaluate the effects of lncRNA PTV1 on colon cancer proliferation and migration via the Wnt6/ß-catenin2 pathway. Materials and Methods: A total of 117 colon cancer and normal adjacent tissue samples were collected. LncRNA PVT1 and miR-1207-5p expressions in these samples and colon cancer cell lines were detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). LncRNA PVT1-silencing cells and miR-1207-5p-overexpressing Caco-2-siPVT1 cells were constructed, respectively. The effects of lncRNA PVT1 silencing on cell proliferation were assessed by MTT and colony formation assays. The effects on invasion and migration were tested by Transwell and scratch assays respectively. The targeting regulatory relationship between miR-1207-5p and Wnt6 was analyzed by a dual-luciferase reporter assay. The relationship between lncRNA PVT1 and miR-1207-5p was studied by RNA-binding protein immunoprecipitation and RNA pull-down assays. The expressions of proteins in the Wnt6/ß-catenin2 pathway were detected by Western blotting. Results: The lncRNA PVT1 mRNA expression in colon cancer tissue was significantly higher than that in normal adjacent tissue (p < 0.05). The expression in lncRNA PVT1-silencing cells was significantly down-regulated (p < 0.05). The colonies of Caco-2-siPVT1 cells decreased, accompanied by a reduced number of cells penetrating Matrigel and migration (p < 0.05). Compared with siPVT1 + NC group, the number of colonies and migration of siPVT1 + miR-1207-5p-overexpressing group increased significantly (p < 0.05). There was a targeting relationship between miR-1207-5p and PVT1. MiR-1207-5p had a targeted binding site with Wnt6. The protein expressions of Wnt6/ß-catenin2 in Caco-2-siPVT1 group were significantly lower than those of control and Caco-2-siNC groups (p < 0.05). Conclusion: LncRNA PVT1 was highly expressed in colon cancer. It may enhance the proliferation and migration of colon cancer cells by up-regulating miR-1207-5p level and enhancing the Wnt6/ß-catenin2 pathway.

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

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

Targeting long non-coding RNA PVT1/TGF-ß/Smad by p53 prevents glioma progression.

Glioma is a primary intracranial malignant tumor with poor prognosis, and its pathogenesis is unclear. This study discussed the impact of p53/lncRNA plasmacytoma variant translocation 1 (lncRNA PVT1)/transforming growth factor beta (TGF-ß)/Smad axis on the biological characteristics of glioma. Glioma and normal tissues were collected, in which relative lncRNA PVT1 and p53 expression was assessed. Pearson's analysis was adopted for the correlation analysis between lncRNA PVT1 and p53. Short interfering RNA (siRNA) against lncRNA PVT1 (siRNA-PVT1), siRNA-p53 or both was transfected into the glioma cells to evaluate effects of lncRNA PVT1 and p53 on cell proliferation, migration, invasion, and apoptosis. Mouse xenograft model of glioma was established to verify function of lncRNA PVT1 and p53 in vivo. Relationship among p53, lncRNA PVT1 and TGF-ß/Smad was predicted and confirmed. Glioma tissues and cells showed downregulated p53 expression and increased lncRNA PVT1 expression. An adverse relationship was noted between p53 expression and lncRNA PVT1 expression. p53 was shown to be enriched in the lncRNA PVT1 promoter region and resulted in its suppression. p53 inhibited glioma cell proliferation, migration, and invasion, and induced apoptosis as well as arrested tumor growth by downregulating lncRNA PVT1. LncRNA PVT1was found to bind to TGF-ß and activate TGF-ß/Smad pathway, promoting progression of glioma. Consequently, p53 exerts anti-oncogenic function on glioma development by suppressing lncRNA PVT1 and subsequently inactivating TGF-ß/Smad pathway.

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.

LncRNA PVT1 facilitates DLBCL development via miR-34b-5p/Foxp1 pathway.

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma and is a very aggressive malignancy with tumor growing rapidly in organs like lymph nodes. The pathogenesis of DLBCL is not clear and the prognosis of DLBCL requires improvement. Here, we investigated the mechanisms of DLBCL, with the focus on lncRNA PVT1/miR-34b-5p/Foxp1 axis. Human DLBCL tissues from diagnosed DLBCL patients and four human DLBCL cell lines, one normal human B lymphoblastoid cell line were used. qRT-PCR and western blotting were employed to measure expression levels of lncRNA PVT1, Foxp1, miR-34b-5p, ß-catenin, and proliferation-related proteins. MTT assay and colony formation assay were performed to determine cell proliferation. Flow cytometry was used to examine cell apoptosis. ChIP and Dual-luciferase assay were utilized to validate interactions of Foxp1/promoters, PVT1/miR-34b-5p and miR-34b-5p/Foxp1. Mouse tumor xenograft model was used to determine the effect of sh-PVT1 on tumor growth in vivo. In this study, we found PVT1 and Foxp1 were elevated in DLBCL tissues and cells while miR-34b-5p was decreased. Knockdown of PVT1, overexpression of miR-34b-5p, or Foxp1 knockdown repressed DLBCL cell proliferation but enhanced cell apoptosis. PVT1 directly bound miR-34b-5p to disinhibit Foxp1/ß-catenin signaling. Foxp1 regulated CDK4, CyclinD1, and p53 expression via binding with their promoters. Knockdown of Foxp1 partially reversed the effects of miR-34b-5p inhibitor on DLBCL cell proliferation and apoptosis. Inhibition of PVT1 through shRNA suppressed DLBCL tumor growth in vivo. All in all, lncRNA PVT1 promotes DLBCL progression via acting as a miR-34b-5p sponge to disinhibit Foxp1/ß-catenin signaling.

The lncRNA PVT1/miR-423-5p axis is positively correlated with the severity of bronchial asthma.

Bronchial asthma (BA) is a serious problem affecting the quality of life of patients. Long noncoding RNAs (lncRNAs) are involved in BA. This study set out to investigate expressions of PVT1/miR-423-5p in the serum of BA patients and its clinical value on BA diagnosis and evaluation. This study included the same number (N = 100) of patients with BA at remission (BA-R), BA at exacerbation (BA-E), and healthy controls. PVT1 level was increased in BA-R and BA-E patients, and PVT1 level was higher in BA-E patients than BA-R patients. miR-141-3p targeted PVT1. miR-423-5p was downregulated in the serum of BA patients and was negatively correlated with PVT1. Area under ROC curve of PVT1/miR-423-5p axis on BA-R patients was 0.837 with sensitivity 0.74, specificity 0.84, while that of BA-E was 0.974 with sensitivity 0.87 and specificity 0.95. PVT1/miR-423-5p axis was negatively correlated with FEV1/FVC, FEV1% pred, and IL-10, and positively correlated with IgE, TNF-α, and IL-6. PVT1 and PVT1/miR-423-5p axis were associated with increased severity while miR-423-5p axis was negatively associated with BA severity. In conclusion, increased levels of PVT1/miR-423-5p had higher diagnostic efficiency on BA patients, especially patients with acute exacerbation.

The lncRNA PVT1/miR-423-5p axis is positively correlated with the severity of bronchial asthma

Bronchial asthma (BA) is a serious problem affecting the quality of life of patients. Long noncoding RNAs (lncRNAs) are involved in BA. This study set out to investigate expressions of PVT1/miR-423-5p in the serum of BA patients and its clinical value on BA diagnosis and evaluation. This study included the same number (N = 100) of patients with BA at remission (BA-R), BA at exacerbation (BA-E), and healthy controls. PVT1 level was increased in BA-R and BA-E patients, and PVT1 level was higher in BA-E patients than BA-R patients. miR-141-3p targeted PVT1. miR-423-5p was downregulated in the serum of BA patients and was negatively correlated with PVT1. Area under ROC curve of PVT1/miR-423-5p axis on BA-R patients was 0.837 with sensitivity 0.74, specificity 0.84, while that of BA-E was 0.974 with sensitivity 0.87 and specificity 0.95. PVT1/miR-423-5p axis was negatively correlated with FEV1/FVC, FEV1% pred, and IL-10, and positively correlated with IgE, TNF-α, and IL-6. PVT1 and PVT1/miR-423-5p axis were associated with increased severity while miR-423-5p axis was negatively associated with BA severity. In conclusion, increased levels of PVT1/miR-423-5p had higher diagnostic efficiency on BA patients, especially patients with acute exacerbation (AU)

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

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