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The current research was aimed at probing into the role of long noncoding RNA (lncRNA) PVT1 in the pathogenesis of glioma and the regulatory mechanism of PVT1/miR-128-3p/ GREM1 network in glioma via regulation of the bone morphogenetic protein (BMP) signaling pathway. Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. Real-time quantitative polymerase chain reaction, Western blot, MTT assay, flow cytometry, migration and invasion assays, and xenograft tumor model were utilized to examine the influence of the lncRNA PVT1/miR-128-3p/ GREM1 network on the biological functions of glioma cells. Luciferase assay and RNA-binding protein immunoprecipitation assay were used to validate the miR-128-3p-target relationships with lncRNA PVT1 or GREM1. In addition, the impact of GREM1 on BMP signaling pathway downstream proteins BMP2 and BMP4 was detected via Western blot. LncRNA PVT1 was highly expressed in human glioma tissues and significantly associated with WHO grade (I–II vs III–IV; p  < 0.05). There existed a regulatory relationship between lncRNA PVT1 and miR-128-3p as well as that between miR-128-3p and GREM1 . MiR-128-3p was downregulated, whereas GREM1 was upregulated in glioma tissues in comparison with para-carcinoma tissues. Overexpression of GREM1 promoted the proliferation and metastatic potential of glioma cells, whereas miR-128-3p mimics inhibited the glioma cell activity through targeting GREM1. Furthermore, lncRNA PVT1 acted as a sponge of miR-128-3p and, thus, influenced the BMP signaling pathway downstream proteins BMP2 and BMP4 through regulating GREM1 . LncRNA PVT1 modulated GREM1 and BMP downstream signaling proteins through sponging miR-128-3p, thereby promoting tumorigenesis and progression of glioma.

Background Our study aimed to investigate the role of lncRNA PVT1 in cervical squamous cell carcinoma. Materials and methods A total of 156 patients with cervical squamous cell carcinoma were enrolled in this study and human papillomavirus (HPV) infection was detected by highly sensitive PCR techniques. Serum levels of PVT1 in patients infected with different HPVs and healthy controls was detected by qRT-PCR and compared. Serum levels of PVT1 were also compared among patients with different sizes of tumor. ROC curve analysis was performed to evaluate the diagnostic values of serum for cervical squamous cell carcinoma. Survival curves were plotted by Kaplan–Meier method and compared to evaluate the prognostic values of serum PVT1 for this disease. Effects of PVT1 siRNA silencing and overexpression on proliferation of cervical squamous cell carcinoma cells were explored by CCK-8 assay. Western blot was performed to detect the expression of TGF-β1 after PVT1 siRNA silencing and overexpression. Results No significant differences in serum levels of PVT1 were detected among patients infected with different HPVs and HPV-negative patients. However, serum levels of PVT1 were significantly higher in all patient groups than in healthy control group. Serum level of PVT1 increased with the increased sizes of primary tumor. Serum PVT1 accurately predicted the disease and its prognosis. PVT1 siRNA silencing inhibited the proliferation of cancer cells and reduced the expression of TGF-β1, while PVT1 overexpression played an opposite role. Conclusion LncRNA PVT1 promotes the growth HPV positive and negative cervical squamous cell carcinoma by inhibiting TGF-β1.

Background Cervical cancer is one of the most frequent malignancies among females worldwide. Increasing evidence have indicated the participation of long noncoding RNAs (lncRNAs) in the progression and metastasis of cervical cancer. Our present study was conducted to explore the effects of lncRNA plasmacytoma variant translocation 1 (PVT1) on the progression of cervical cancer and the underlying mechanisms. Materials and methods Expressions of PVT1, miR-140-5p and Smad3 in cervical cancer cell lines were detected by qRT-PCR and western blotting. Bioinformatics analysis and luciferase assays were used to elucidate the potential correlations between PVT1, miR-140-5p and Smad3. The roles of PVT1 on the progression of cervical cancer cells were determined by transfecting sh-RNA through series function assays such as colony formation assay, wound healing assay, transwell assay. Results PVT1 and Smad3 were upregulated, and miR-140-5p was downregulated in cervical cancer cells. PVT1 could bind directly with miR-140-5p, and Smad3 was a downstream target of miR-140-5p. Inhibition of PVT1 could enhance expression of miR-140-5p, inhibit the expression of Smad3, significantly inhibited the proliferation, migration, invasion in cervical cancer cells. While transfection of miR-140-5p inhibitor could partially reverse the above changes in cervical cancer cells. Conclusions The results revealed that PVT1 could promote the proliferation and metastasis via increasing the Smad3 expression by sponging miR-140-5p, which might be a promising prognostic and therapeutic target for cervical cancer.

Long noncoding RNA (LncRNA) PVT1 has recently been reported to be involved in the development of hepatocellular carcinoma (HCC). We aimed to elucidate the correlation of PVT1 with hepatitis B virus-positive HCC in the clinic, and the roles of PVT1 in liver cancer cell biology, as well as to investigate the underlying molecular mechanisms. qPCR analysis was performed to examine the expression of PVT1 in hepatitis B virus-positive HCC tissues and liver cancer cell lines. lncRNA PVT1 overexpression and knockdown were achieved by transfection of an overexpression vector or shRNA. Cell proliferation, colony formation, migration, apoptosis, and invasion capabilities were examined, accordingly. RNA pull-down assay was employed to examine the connection between PVT1 and the PRC2 complex. Chromatin immunoprecipitation was employed to test the combination with EZH2 protein and H3K27me3 level on the MYC promoter. The results revealed that upregulation of PVT1 was detected in hepatitis B virus-positive HCC tissues compared with that noted in the HBV-negative samples. lncRNA PVT1 enhanced cell proliferation, migration, and invasion in the hepatitis B virus-positive Hep3B cells rather than the hepatitis B virus-negative HepG2 cells. PVT1 was able to bind EZH2 and obstruct the recruitment of EZH2 to the promoter of MYC therefore promoting MYC expression by altering H3K37me3 status in Hep3B liver cancer cells, and EZH2 protein was negatively correlated with lncRNA-PVT1 expression. In conclusion, our results indicate that lncRNA PVT1 promotes hepatitis B virus-positive liver cancer progression by disturbing histone methylation on the MYC promoter, suggesting that lncRNA PVT1 may be a potential target for developing diagnostic and therapeutic strategies of hepatitis B virus-positive liver cancer at the early stages.

Oral squamous cell carcinoma (OSCC) is a cancer with high morbidity and mortality. Research has demonstrated that long non-coding RNAs (lncRNAs) are critical for tumor initiation and development. In the present study, we aimed to ascertain the functions and potential mechanisms of lncRNA plasmacytoma variant translocation 1 (PVT1) in OSCC. Firstly, we found that the expression of PVT1 was increased in human OSCC tumor tissues and it was related to reduced survival of the patients. Furthermore, miR-150-5p expression was downregulated in OSCC tumor tissues and it was negatively related with PVT1. Moreover, GLUT-1 protein expression was upregulated in human OSCC tumor tissues. In addition, cell proliferation capacity was measured by CCK-8 assay and cell invasion and migration were measured by Transwell assay. PVT1 overexpression promoted cell proliferation, invasion and migration, while these effects were abrogated by PVT1 downregulation. In addition, luciferase gene reporter assay verified the miR-150-5p directly binds with PVT1, which regulates the biological functions of OSCC. Additionally, luciferase gene reporter assay confirmed that GLUT-1 was a target for miR-150-5p. The promotion of cell proliferation, invasion and migration in LV-PVTl-transfected cells was eliminated following miR-150-5p overexpression. Finally, in vivo nude mouse xenograft model further verified that PVT1 knockdown inhibited tumor growth, formation, invasion and migration. According to the results, PVT1 is increased in human OSCC tumor tissues, and is related to the poor prognosis of human OSCC patients. We uncovered a previously unappreciated PVTl/miR-150-5p/GLUT-l signaling axis that promotes cell proliferation, invasion, migration and inhibits apoptosis in OSCC cell lines and in vivo, which suggests that this axis could be a target for the treatment of OSCC.

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-1β) 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.

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-1β 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.

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention.

The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been identified as an oncogene in numerous diseases, and aberrant lncRNA PVT1 expression has been associated with the development of cancer. However, the underlying mechanism by which lncRNA PVT1 affects cell invasion in esophageal cancer has been not demonstrated. In the current study, the expression of lncRNA PVT1 was found to be increased in esophageal cancer specimens (n=77) by reverse transcription-quantitative polymerase chain reaction, and was correlated with tumor stage (P=0.009) and metastasis (P<0.001). In vitro, by using transwell assay, upregulation of lncRNA PVT1 promoted the invasion of TE-1 esophageal cancer cells; while downregulation of lncRNA PVT1 inhibited Eca-109 cell invasion. In addition, western blot analysis indicated that upregulation of lncRNA PVT1 may induce epithelial-to-mesenchymal transition (EMT) by regulating the expression levels of EMT markers (E-cadherin, N-cadherin and vimentin). In conclusion, lncRNA PVT1 is able to regulate the invasion of esophageal cancer cells by inducing EMT.