lncRNA PVT1 Expression Research Articles

Overcoming Breast Cancer Treatment Resistance with Optimizing Sonodynamic Therapy and Radiation Sensitizers on lncRNA PVT1 and miR-1204 Expression.

Acoustic cavitation is a foundational mechanism in ultrasound therapy, primarily through inertial cavitation resulting from microbubble collapse. Sonodynamic therapy, with inertial acoustic cavitation threshold and low-dose radiation in the presence of sensitizers, may provide significant effects for cancer treatment, potentially overcoming resistance encountered with single therapies. MCF7 breast cancer cells were subjected to sonodynamic therapy either alone or combined with ionizing radiation, gold nanoparticles coated with apigenin, and methylene blue. Several parameters were evaluated, including reactive oxygen species (ROS) generation and colonization. Additionally, the investigation included assessing the long non-coding RNA (lncRNA) PTV1 with miRNA1204 and related genes using Real-Time PCR. Sonodynamic therapy at a mechanical index of 0.31 as acoustic cavitation threshold increased intracellular ROS. Combining sonodynamic therapy and 2Gy X-ray radiation with methylene blue and gold nanoparticles coated with apigenin significantly decreased plating efficiency (4.44±1.69), and survival fraction (2.75±1.98) compared with control (Ctrl.) (98.77±4.49) and (97.59± 2.94), respectively. This was associated with a marked increase in ROS with a mean fluorescence intensity of 20576.2 ± 4.6 (>4.5 times). The combined treatment also increased p53 expression and decreased the expression of PVT1, miR-1204, and related genes. Sonodynamic therapy in inertial acoustic cavitation threshold, combined with ionizing radiation in the presence of biocompatible nanoparticles, could enhance the therapeutic effects on the miR-1204, derived from lncRNA PVT1, that functions as an oncogenic microRNA in breast cancer. This approach has the potential to overcome treatment resistance encountered with single therapies.

Upregulation of the long noncoding RNA GJA9-MYCBP and PVT1 is a potential diagnostic biomarker for acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common type of blood cancer in children. Aberrant expression of long noncoding RNAs (lncRNAs) may set stages for ALL development. LncRNAs are emerging as a novel diagnostic and prognostic biomarker for ALL. Herein, we aimed to evaluate the expression of lncRNA GJA9-MYCBP and PVT1 in blood samples of ALL and healthy individuals. As a case-control study, 40 pairs of ALL and healthy individual samples were used. The expression of MYC and each candidate lncRNA was measured using quantitative real-time PCR. Any possible association between the expression of putative noncoding RNAs and clinicopathological characteristics was also evaluated. LncRNA GJA9-MYCBP and PVT1 were significantly upregulated in ALL samples compared with healthy ones. Similarly, mRNA levels of MYC were increased in ALL samples than control ones. Receiver operating characteristic curve analysis indicated a satisfactory diagnostic efficacy (p-value <.0001), suggesting that lncRNA GJA9-MYCBP and PVT1 may serve as a diagnostic biomarker for ALL. Linear regression analysis unveiled positive correlations between the expression level of MYC and lncRNA GJA9-MYCBP and PVT1 in ALL patients (p-values <.01). In this study, we provided approval for the clinical diagnostic significance of lncRNA GJA9-MYCBP and PVT1that their upregulations may be a diagnostic biomarker for ALL.

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

[This retracts the article DOI: 10.2147/OTT.S233149.].

Knockdown of lncRNA PVT1 protects human trabecular meshwork cells against H2O2-induced injury via the regulation of the miR-29a-3p/VEGF/MMP-2 axis

PurposeHuman trabecular meshwork cell (HTMC) dysfunction results in imbalanced aqueous humor inflow and outflow, leading to an increase in intraocular pressure (IOP). Uncontrolled high IOP can promote the occurrence of glaucoma, an irreversible optic neuropathy. Here, we explored whether the long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1)/microRNA-29a-3p (miR-29a-3p) axis could ameliorate HTMC dysfunction under oxidative stress by modulating the expression of the proangiogenic factor vascular endothelial growth factor (VEGFA) and the profibrotic factor metalloproteinase-2 (MMP-2). MethodsHTMCs were cultured under H2O2-induced oxidative stress for 48 h. The expression of lncRNA PVT1, miR-29a-3p, VEGFA, MMP-2, intracellular adhesion molecule-1 (ICAM-1), and alpha-smooth muscle actin (α-SMA) was detected by reverse transcription quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. Interference experiments were conducted via the transfection of HTMCs with small interfering RNA (siRNA) targeting lncRNA PVT1 or miR-29a-3p mimics. A luciferase reporter assay was undertaken to identify the presence of a miR-29a-3p binding site in lncRNA PVT1. Flow cytometry and Transwell and Cell Counting Kit-8 assays were employed to evaluate HTMC functions under oxidative stress with different treatments. ResultsIn HTMCs, the expression of lncRNA PVT1 was induced by H2O2 treatment, whereas that of miR-29a-3p was inhibited. The levels of angiogenic factors (VEGFA, ICAM-1) and fibrosis-associated mediators (MMP-2, α-SMA) were upregulated in HTMCs under oxidative stress. The siRNA-mediated suppression of lncRNA PVT1 or the upregulation of miR-29a-3p significantly suppressed the expression of VEGFA, MMP-2, ICAM-1, and α-SMA. A luciferase reporter assay confirmed that lncRNA PVT1 directly targeted miR-29a-3p and acted as a miR-29a-3p sponge. The knockdown of lncRNA PVT1 restored the level of miR-29a-3p in H2O2-treated HTMCs, thereby inhibiting VEGFA and MMP-2, its target mRNAs. HTMC dysfunction, including increased apoptosis and decreased cell mobility and viability, could be effectively ameliorated by lncRNA PVT1 downregulation or miR-29a-3p overexpression under oxidative stress. ConclusionLncRNA PVT1 has potential as a therapeutic target for inhibiting VEGFA and MMP-2, thus protecting HTMCs, suppressing the progression of fibrosis, and, consequently, improving the outcome of glaucoma filtration surgery.

Expression level and clinical significance of LncRNA PVT1 in the serum of patients with LEASO.

Our study aims to investigate the long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) in lower extremity arteriosclerosis obliterans (LEASO) patient serum and its clinical significance in LEASO. From July 2021 to April 2022, 133 LEASO patients diagnosed at the Qingdao Municipal Hospital were included. Among them, 44 complicated with coronary artery disease (CAD) were classified as the LEASO with CAD group. The remaining 89 were marked as the LEASO group, which was classified into single (n=48) and double (n=41) lower limb groups, with the former being subclassified into the left (n=28) and right (n=20) lower limb groups based on the affected sites. Fifty healthy individuals who came to our hospital for physical examination during the same period were randomly included and defined as the Healthy Control group. PVT1 expression was detected in serum samples from each group using a quantitative reverse transcriptase-polymerase chain reaction , and differences in expression levels were calculated. The ankle-brachial index (ABI) of patients in the LEASO group was measured using a sphygmomanometer, and its correlation with PVT1 was analyzed. Clinical data and laboratory test results (including blood routine, liver and renal function, and blood lipids) were collected for all patients upon admission. Logistic regression analyses were performed to determine the influence of PVT1 and laboratory test results on LEASO. The diagnosis and prediction of LEASO were obtained by combing PVT1 with laboratory test indicators. It was found that lncRNA PVT1 expression was the highest in the serum of the LEASO with CAD group, followed by the LEASO and control groups (P < 0.05). Within the LEASO group, no significant difference in PVT1 expression was seen between the left and right limbs (P > 0.05), nor between the single and double lower limb groups. Furthermore, the PVT1 expression increased with the Rutherford grades, indicating a negative correlation between PVT1 and ABI. Logistic regression analysis revealed that triglycerides (OR = 2.972, 95% CI [1.159-7.618]), cholesterol (OR = 6.655, 95% CI [1.490-29.723]), C-reactive protein (OR = 1.686, 95% CI [1.218-2.335]), and PVT1 (OR = 2.885, 95% CI [1.350-6.167]) were independent risk factors for LEASO. Finally, strong sensitivity was observed in the receiver operating characteristic curve when combining PVT1 with meaningful laboratory indicators to diagnose and predict LEASO. lncRNA PVT1 promotes LEASO occurrence and progression and is related to atherosclerosis severity. The expression of PVT1 was negatively correlated with ABI. Logistic regression analysis suggested that blood lipid levels and inflammatory reactions might be related to LEASO occurrence. PVT1 was incorporated into laboratory indicators to predict LEASO. The subject's working curve area was large, and the prediction results were highly sensitive.

LncRNA PVT1 promotes strong stemness and endothelial progenitor cell characteristics in renal carcinoma stem cells.

Renal cancer stem cells (RCSCs) derived from clear cell renal cell carcinoma (ccRCC) tissues with higher microvessel density (MVD) have strong stemness and endothelial progenitor cells-like (EPCs-like) characteristics. A high level of lncRNA PVT1 expression is essential for simultaneously retaining strong RCSC stemness and EPCs-like characteristics. PVT1 binds with TAZ protein and prevents its phosphorylation, which promotes RCSC stemness. Moreover, RCSCs support endothelial differentiation and angiogenesis, which are mediated via the PVT1/miR-15b/KDR axis. This report provides insight into the determinants of RCSC impact on stemness and highlights the critical role of RCSC in angiogenesis. The presented findings suggest that targeting RCSC through PVT1 expression may be a new treatment strategy for ccRCC.

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

BackgroundPlasmacytoma 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. PurposeWe aimed to explore the interaction between lncRNA PVT1 and STAT5B in BC tumorigenesis and find potential drugs for BC. MethodsThe 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. ResultsLncRNA 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. ConclusionsWe first identified the lncRNA PVT1/STAT5B positive feedback loop for bladder carcinogenesis, and found a potentially effective drug for BC.

Effect of lncRNA pvt1 on HBV replication in HepG2.2.15 cells, and its possible mechanism of action

Purpose: To investigate the influence of lncRNA pvt1 on hepatitis B virus replication in HepG2.2.15 cells and the underlying mechanism of action. &#x0D; Methods: Concentrations of lncRNA pvt1 in HBV-positive liver cancer cell lines (HepAD38+, HepG2.2.15+, HepG2+, and HepaRG+), and 3 HBV-negative liver cancer cell lines were determined and compared. Differences in HBV DNA content, levels of HBsAg and HBeAg, and STAT3 axis signal pathway among groups were evaluated. &#x0D; Results: LncRNA pvt1 levels in HBV-positive hepatoma cells were significantly higher than the corresponding expression levels in HBV-negative hepatoma cells. after si-pvt1 treatment in HepG2.2.15 cells, the 3.2K HBV DNA content increased significantly (p &lt; 0.05), and the expression levels of HBsAg and HBeAg in HepG2.2.15 cells also significantly increased. In all groups, STAT3 protein level was comparable, but p-STAT3 protein expression in si-pvt1 group was significantly reduced, relative to those in Si NC and control groups (p &lt; 0.05). &#x0D; Conclusion: Levels of lncRNA pvt1 expression in HBV-positive and HBV-negative hepatoma cells differ significantly. Treatment with si-pvt1 decrease HBV DNA content in HepG2.2.15 cells through a mechanism that relates to the STAT3 axis signal pathway. This finding may be beneficial for follow-up treatment of HBV.

Long non-coding RNA PVT1 promotes the proliferation, migration and EMT process of ovarian cancer cells by regulating CTGF.

Ovarian cancer remains one of the most common gynecological malignancies with a poor prognosis. The present study investigated the roles of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) in the regulation of the malignant phenotype of ovarian cancer cells, including cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). SKOV3 and CAOV3 cells were transfected with small interfering RNA (siRNA) targeting lncRNA PVT1 (si-PVT1) or control siRNA and the si-PVT1 transfected cells were co-cultured with recombinant human connective tissue growth factor (rhCTGF). The proliferation, migration and invasion abilities of the cells were examined via Cell Counting Kit-8, colony formation, wound-healing and Transwell assays. The relative expression levels of lncRNA PVT1, CTGF, E-cadherin and vimentin were analyzed using reverse transfection-quantitative polymerase chain reaction, and western blotting was employed to detect the protein levels of CTGF, E-cadherin and vimentin. The expression of lncRNA PVT1 was significantly reduced in SKOV3 and CAOV3 cells following transfection with si-PVT1. In addition, the proliferation, migration and invasion abilities of SKOV3 and CAOV3 cells were repressed following lncRNA PVT1 knockdown. The knockdown of lncRNA PVT1 also reduced the expression of CTGF and vimentin, and increased the expression of E-cadherin. The changes in the proliferation, migration and invasion of the cells induced by transfection with si-PVT1 were partially attenuated in the presence of rhCTGF. Furthermore, co-culture with rhCTGF reversed the si-PVT1-induced changes in the expression of EMT-associated proteins. In conclusion, lncRNA PVT1 promotes the proliferation, migration, invasiveness and EMT process of ovarian cancer cells, and CTGF contributes to the effect of lncRNA PVT1.

The Effect of lncRNA-PVT1 on Liver Cancer Rats by Regulating the Expression of MMP9.

As a malignant tumor, liver cancer has a high lethality rate. The research on the pathogenesis of liver cancer is the key to the treatment of liver cancer. The latest research claims that lncRNA-PVT1 as a tumor gene participates in the generation and development of tumors by regulating matrix metalloproteinase MMP9. The purpose of this article is to explore the specific effect and mechanism of lncRNA-PVT1 on liver cancer rats by regulating the expression of MMP9. In this article, 50 rats are used as experimental subjects, the rats are divided into control group and observation group, and the liver cancer cell line HepG2 is cultured. The transplanted tumor liver cancer model was constructed by transfection of hair, the expression of lncRNA-PVT1 in the observation group was reduced by knockdown method, the expression levels and changes of lncRNA-PVT1 and MMP9 in the two groups were detected by PCR fluorescence method, and the difference between lncRNA-PVT1 and MMP9 was analyzed. The MTT method was used to detect the proliferation, migration, and invasion capabilities of the two groups of liver cancer cells (LCC) and to explore the effect of lncRNA-PVT1 on rat LCC by regulating the expression of MMP9. The results of the study showed that after knocking down the expression of lncRNA-PVT1 in the observation group, the expression of MMP9 also decreased. At the same time, the migration rate of LCC HepG2 decreased by 27.4%, the level of invasion ability decreased by 21.6%, and the proliferation rate of LCC decreased by 17.8%. Therefore, it can be seen that lncRNA-PVT1 plays a positive regulatory role on the expression of MMP9, and the expression of MMP9 promotes the proliferation, migration, and invasion of rat LCC.

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

ABSTRACT 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-β)/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-β/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-β and activate TGF-β/Smad pathway, promoting progression of glioma. Consequently, p53 exerts anti-oncogenic function on glioma development by suppressing lncRNA PVT1 and subsequently inactivating TGF-β/Smad pathway.

Role and Mechanism of lncRNA-pvt1 in the Pathogenesis of Acute Lymphoblastic Leukemia in Children.

Objective To investigate the role and mechanism of lncRNA-pvt1 in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). Methods The expression of lncRNA-pvt1 in bone marrow tissues of ALL patients after initial diagnosis and complete remission was detected by RT-PCR to explore its possible involvement in the pathogenesis of ALL. The proliferation and apoptosis of Jurkat cells transfected with lncRNA-pvt1 were observed by MTT and flow cytometry. Results lncRNA-pvt1 expression was upregulated in bone marrow of ALL patients. Knockdown of lncRNA-pvt1 inhibited Jurkat cell proliferation and increased its apoptosis rate. Conclusion Silencing lncRNA-pvt1 expression can inhibit the development of ALL.

Up-regulated lncRNA-PVT1 expression in peripheral blood mononuclear cells of patients with coronary artery disease is correlated with decreased interleukin-10 production.

Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA, which has not been previously studied in the inflammatory responses of the peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD). This cross-sectional study was conducted on 15 CAD patients and 15 non-CAD (NCAD) individuals. The PVT1 expression was assessed in the PBMCs of the participants using a real-time polymerase chain reaction. Interleukin (IL)-10, IL-22, and matrix metalloproteinase-9 (MMP-9) were measured in the plasma and supernatant of cultured PBMCs in the presence or absence of lipopolysaccharide (LPS) using flow cytometry and enzyme-linked immunosorbent assay. An increased expression of PVT1 was observed in the untreated PBMCs of CAD patients, compared to the NCAD group. The PVT1 was significantly up-regulated after LPS treatment in the PBMCs of both groups. Plasma MMP-9 levels were found to be higher in CAD patients than in the control individuals. The level of IL-10 and IL-22 production by the non-treated PBMCs of CAD cases was significantly lower than the NCAD group. Overall, in the examined population, PVT1 expression was negatively correlated with IL-10 secretion. Moreover, the results showed a significant negative correlation between PVT1 expression and IL-10 production by untreated cells. The PVT1 expression augmented in the PBMCs of CAD patients, which could be associated with the decreased IL-10 generation by the PBMCs of these patients.

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

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

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

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

Methionine deficiency promoted mitophagy via lncRNA PVT1-mediated promoter demethylation of BNIP3 in gastric cancer.

The occurrence of recurrence and metastasis after treatment is a major challenge in the treatment of gastric cancer. This study was based on the methionine (Met)-dependent characteristics of gastric cancer cells to explore the effect of Met deficiency on the occurrence and development of gastric cancer. Human gastric cancer cell lines MKN45 and AGS and nude mice model were used to explore how Met affects gastric cancer by regulating lncRNA PVT1. The levels of lncRNA PVT1 in gastric cancer cells and human gastric cancer xenografts of nude mice were down-regulated under the condition of Met deficiency. The cell viability and cell proliferation were declined after MKN45 and SGC-790 cells were cultured in Met-deficient medium. LncRNA PVT1 could affect BNIP3 promoter DNA methylation level through its interaction with DNMT1. Moreover, the silence of lncRNA PVT1 and the up-regulation of BNIP3 level inhibited the gastric cancer cell proliferation. Met deficiency could up-regulate BNIP3 expression by inhibiting the binding of lncRNA PVT1 to DNMT1, and activate mitophagy, thus inhibiting gastric cancer cell proliferation. Our study suggested that Met deficiency could down-regulate the expression of lncRNA PVT1, further demethylated the promoter of BNIP3, thus inhibiting the proliferation of gastric cancer cells by activating mitophagy.

Effects of inhibiting the expression of lncRNA PVT1 on the proliferation, apoptosis and oxidative stress of vascular endothelial cells induced by hyperglycemia

Objective: To investigate the effects of inhibition of lncRNA PVT1 on the proliferation, apoptosis and oxidative stress of vascular endothelial cells induced by hyperglycemic. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and divided into four groups: control group (5.5 mmol/L glucose), high glucose group (30 mmol/L glucose), high glucose + siNC group (30 mmol/L glucose +siNC, negative control group), HG + siPVT1 group (30 mmol/L glucose + siPVT1, lncRNA PVT1 silencing group). The expression of PVT1 after transfection was detected by quantitative real-time PCR. MTT assay was used to detect the effect of siPVT1 (small interfering RNA PVT1) on the proliferation of HUVECs cells induced by high glucose. Flow cytometry was used to detect ROS and apoptosis of HUVECs cells induced by siPVT1. Western blot was used to detect the expression levels of apoptotic proteins such as Bax, Bcl-2, and cleaved caspase-3 in HUVECs cells. Results: Compared with the control group, after transfection with siPVT1, the expression level of PVT1 was decreased significantly (P＜0.05). MTT results showed that the proliferation activity of HUVECs cells in the high-glucose group was reduced significantly after 24 h and 48 h. Compared with the HG + siNC group, the proliferation activity of HUVECs cells in the HG + siPVT1 group was increased significantly (P＜0.05) after 24 h and 48 h. Flow cytometry results showed that ROS and apoptosis rate of HUVECs cells in the high-glucose group were increased significantly compared with the control group. Compared with the HG + siNC (negative control) group, ROS and apoptosis rates of HUVECs cells in the HG + siPVT1 group were reduced significantly. Compared with the control group, the expression levels of cleaved-caspase-3 and Bax in the high-glucose group were significantly up-regulated, while the expression level of Bcl-2 was down-regulated. Compared with the HG + siNC group, the expression levels of cleaved-caspase-3 and Bax were down-regulated, and the expression level of Bcl-2 was up-regulated. The differences were statistically significant (P＜0.05). Conclusion: Inhibition of lncRNA PVT1 can significantly increase the proliferation activity of HUVECs cells induced by hyperglycemia, reduce oxidative stress and inhibit cell apoptosis.

Effect of lncRNA PVT1/miR186/KLF5 Axis on the Occurrence and Progression of Cholangiocarcinoma.

This study primarily focused on the effect of the long noncoding RNA (lncRNA) PVT1/miR186/KLF5 axis on the occurrence and progression of cholangiocarcinoma (CCA). miR186 was found both in the lncRNA PVT1 targeting miRNAs and KLF5 targeting miRNAs using bioinformatic analysis. The expression of lncRNA PVT1 and KLF5 in the TFK-1, QBC939, and HuCCT1 cell lines and normal biliary epithelial HIBEpiC cells was detected by RT-qPCR. The significance of lncRNA PVT1 and KLF5 on cell proliferation was analyzed using the MTT assay and clone formation assay in lncRNA PVT1 and KLF5 silencing HuCCT1 cell lines and lncRNA PVT1and KLF5 overexpressing TFK-1 and QBC939 cell lines, respectively. The potential role of lncRNA PVT1 and KLF5 in cell migration was detected using the transwell invasion assay in CCA cell lines and tumor formation assay. Additionally, lncRNA PVT1 and KLF5 were proved to be highly expressed in CCA tissues and cell lines. Silencing and overexpressing of lncRNA PVT1 or KLF5 markedly inhibited or increased the cell proliferation and cell invasion in CCA cell lines, respectively. Silencing and overexpressing of lncRNA PVT1 significantly inhibited and increased the expression of KLF5 in CCA cell lines, respectively. Silencing of lncRNA PVT1 increased the expression of miR186, and silencing of miR186 increased the expression of KLF5 in CCA cell lines. Cotransfection of lncRNA PVT1 and miR186 increased the expression of KLF5 compared with controls. Overall, these results demonstrated that the lncRNA PVT1/miR186/KLF5 axis might exert a key role in the occurrence and progression of CCA, and this axis might provide a new target for treating CCA.

Long non-coding RNA Pvt1 modulates the pathological cardiac hypertrophy via miR-196b-mediated OSMR regulation

Cardiac hypertrophy is the uppermost risk factor for the development of heart failure, leading to irreversible cardiac structural remodeling and sudden death. As a major mediator of cardiac remodeling, oncostatin M (OSM) and its receptor, OSMR, attract plenty of interest. Recent studies have demonstrated key effects of noncoding RNAs on myocardial remodeling. However, whether noncoding RNAs that regulate the expression of OSMR would regulate the process of remodeling remain unclear. Herein, we observed that long noncoding RNA (lncRNA) Pvt1 expression showed to be significantly elicited by aortic banding (AB) operation in vivo and by angiotensin (Ang II) treatment in vitro. Pvt1 knockdown significantly attenuated the myocardial hypertrophy caused by pressure overload within rats and the cardiac myocyte hypertrophy caused by Ang II in vitro. Moreover, Pvt1 knockdown also decreased cellular myomesin and B-raf, which was involved in OSM function in cardiac remodeling. Based on online tools prediction, miR-196b may simultaneously target Pvt1 and OSMR 3′ untranslated region (UTR). In rat H9c2 cells and primary cardiac myocyte, Pvt1 and miR-196b exerted negative regulatory effects on each other and miR-196b negatively regulated OSMR expression. Pvt1 directly targeted miR-196b to relieve miR-196b-induced OSMR suppression via acting as a competing endogenous RNA (ceRNA). Moreover, the effect of miR-196b suppression upon the B-raf was opposite to Pvt1 knockdown, and miR-196b suppression might significantly attenuate the effect of Pvt1 knockdown. In summary, Pvt1/miR-196b axis modulating cardiomyocyte hypertrophy and remodeling via OSMR. Our findings provide a rationale for further studies on the potential therapeutic benefits of Pvt1 function and mechanism in cardiac and cardiomyocyte hypertrophy by a lncRNA-miRNA-mRNA network.

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

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