Topic
PVT1
About: PVT1 is a research topic. Over the lifetime, 190 publications have been published within this topic receiving 7307 citations. The topic is also known as: LINC00079 & NCRNA00079.
Papers published on a yearly basis
Papers
TL;DR: Bagchi et al. as mentioned in this paper investigated the role of a nearby long non-coding RNA gene, PVT1, that tends to be co-amplified.
Abstract: Pvt1 overexpression in mice contributes to high Myc levels due to 8q24.21 gain and to MYC-driven tumorigenesis. Many cancer cells carry extra copies of chromosomal region 8q24.21, encompassing the MYC oncogene. Anindya Bagchi and colleagues have now investigated the role of a nearby long non-coding RNA gene, PVT1, that tends to be co-amplified. They show in engineered mouse models that PVT1 overexpression contributes to high MYC levels due to the 8q24.21 amplifications and to MYC-driven tumorigenesis. MYC and PVT1 levels are also correlated in human tumours, suggesting a similar cooperation. The authors suggest that targeting PVT1 may offer an alternative therapeutic strategy. ‘Gain’ of supernumerary copies of the 8q24.21 chromosomal region has been shown to be common in many human cancers1,2,3,4,5,6,7,8,9,10,11,12,13 and is associated with poor prognosis7,10,14. The well-characterized myelocytomatosis (MYC) oncogene resides in the 8q24.21 region and is consistently co-gained with an adjacent ‘gene desert’ of approximately 2 megabases that contains the long non-coding RNA gene PVT1, the CCDC26 gene candidate and the GSDMC gene. Whether low copy-number gain of one or more of these genes drives neoplasia is not known. Here we use chromosome engineering in mice to show that a single extra copy of either the Myc gene or the region encompassing Pvt1, Ccdc26 and Gsdmc fails to advance cancer measurably, whereas a single supernumerary segment encompassing all four genes successfully promotes cancer. Gain of PVT1 long non-coding RNA expression was required for high MYC protein levels in 8q24-amplified human cancer cells. PVT1 RNA and MYC protein expression correlated in primary human tumours, and copy number of PVT1 was co-increased in more than 98% of MYC-copy-increase cancers. Ablation of PVT1 from MYC-driven colon cancer line HCT116 diminished its tumorigenic potency. As MYC protein has been refractory to small-molecule inhibition, the dependence of high MYC protein levels on PVT1 long non-coding RNA provides a much needed therapeutic target.
691 citations
TL;DR: This study demonstrates that the expression of many lncRNAs is up‐regulated in early liver development and that the fetal liver can be used to search for new diagnostic markers for HCC.
446 citations
TL;DR: It is shown that the PVT1 promoter has a tumor-suppressor function that is independent of PVT 1 lnc RNA, and regulatory sequences of lncRNA genes as potential disease-associated DNA elements are highlighted.
435 citations
TL;DR: The results of this study reveal a potential ceRNA regulatory pathway in which PVT1 modulates HK2 expression by competitively binding to endogenous miR-143 in GBC cells, which may provide new insights into novel molecular therapeutic targets for GBC.
Abstract: The long non-coding RNA PVT1 (lncRNA PVT1) has been reported to act as an oncogenic regulator of several cancers. However, its expression and function in gallbladder cancer (GBC) remain largely unknown. In situ hybridization (ISH) and quantitative real-time PCR (qPCR) were performed to detect the expression of PVT1 and miR-143 in GBC tissues and cell lines. Immunohistochemistry (IHC) assays were performed to assess the expression of the hexokinase 2 (HK2) protein. The relationships among PVT1, miR-143 and HK2 were evaluated using dual-luciferase reporter, RNA immunoprecipitation (RIP) and biotin pull-down assays. The biological functions of PVT1, miR-143 and HK2 in GBC cells were explored with cell counting kit 8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, wound healing and glucose metabolism assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of PVT1 and HK2 on GBC. PVT1 was upregulated in GBC tissues and cells and was positively associated with malignancies and worse overall survival. PVT1 knockdown inhibited cell proliferation, migration, and invasion in vitro and restrained tumor growth in vivo. Further studies demonstrated that PVT1 positively regulated HK2 expression via its competing endogenous RNA (ceRNA) activity on miR-143. Additionally, HK2 expression and function were positively correlated with PVT1. Furthermore, we observed that the PVT1/miR-143/HK2 axis promoted cell proliferation and metastasis by regulating aerobic glucose metabolism in GBC cells. The results of our study reveal a potential ceRNA regulatory pathway in which PVT1 modulates HK2 expression by competitively binding to endogenous miR-143 in GBC cells, which may provide new insights into novel molecular therapeutic targets for GBC.
405 citations
TL;DR: The results suggest that MYC and PVT1 contribute independently to ovarian and breast pathogenesis when overexpressed because of genomic abnormalities, and suggest that PVT 1-mediated inhibition of apoptosis may explain why amplification of 8q24 is associated with reduced survival duration in patients treated with agents that act through apoptotic mechanisms.
Abstract: Purpose: This study was designed to elucidate the role of amplification at 8q24 in the pathophysiology of ovarian and breast cancer because increased copy number at this locus is one of the most frequent genomic abnormalities in these cancers. Experimental Design: To accomplish this, we assessed the association of amplification at 8q24 with outcome in ovarian cancers using fluorescence in situ hybridization to tissue microarrays and measured responses of ovarian and breast cancer cell lines to specific small interfering RNAs against the oncogene MYC and a putative noncoding RNA, PVT1 , both of which map to 8q24. Results: Amplification of 8q24 was associated with significantly reduced survival duration. In addition, small interfering RNA–mediated reduction in either PVT1 or MYC expression inhibited proliferation in breast and ovarian cancer cell lines in which they were both amplified and overexpressed but not in lines in which they were not amplified/overexpressed. Inhibition of PVT1 expression also induced a strong apoptotic response in cell lines in which it was overexpressed but not in lines in which it was not amplified/overexpressed. Inhibition of MYC , on the other hand, did not induce an apoptotic response in cell lines in which MYC was amplified and overexpressed. Conclusions: These results suggest that MYC and PVT1 contribute independently to ovarian and breast pathogenesis when overexpressed because of genomic abnormalities. They also suggest that PVT1 -mediated inhibition of apoptosis may explain why amplification of 8q24 is associated with reduced survival duration in patients treated with agents that act through apoptotic mechanisms.
361 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2026 | 1 |
| 2025 | 20 |
| 2024 | 18 |
| 2023 | 86 |
| 2022 | 84 |
| 2021 | 29 |