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

Guo, Guangcheng; Wang, Fang; Han, Ming; Gu, Yuanting; Duan, Xin; Li, Lin

doi:10.1039/c7ra12042g

Cited by 6 publications

(6 citation statements)

References 30 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PVT1 has been described in other types of cancer to act in the nucleus; thus, in ovarian cancer PVT1 represses miR-214 expression by recruiting EZH2 to its promoter [ 25 ], and in non-small cell lung cancer (NSCLC) PVT1 inhibits the expression of Large Tumor Suppressor Kinase 2 ( LATS2 ) by recruiting EZH2 to the LATS2 promoter [ 26 ]. In other tissues such as breast cancer [ 27 ], hepatocellular carcinoma [ 28 ], gastric cancer [ 29 ], and cholangiocarcinoma [ 30 ], PVT1 has been shown to interact with EZH2 and epigenetically inhibit the expression of some target genes. In fact, no description of PVT1 involvement with large-scale repression of gene expression has been published.…”

Section: Introductionmentioning

confidence: 99%

PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors

et al. 2021

View full text Add to dashboard Cite

Background Androgen receptor (AR) and polycomb repressive complex 2 (PRC2) are known to co-occupy the loci of genes that are downregulated by androgen-stimulus. Long intergenic non-coding RNA (lincRNA) PVT1 is an overexpressed oncogene that is associated with AR in LNCaP prostate cancer cells, and with PRC2 in HeLa and many other types of cancer cells. The possible involvement of PVT1 in mediating androgen-induced gene expression downregulation in prostate cancer has not been explored. Methods LNCaP cell line was used. Native RNA-binding-protein immunoprecipitation with anti-AR or anti-EZH2 was followed by RT-qPCR with primers for PVT1. Knockdown of PVT1 with specific GapmeRs (or a control with scrambled GapmeR) was followed by differentially expressed genes (DEGs) determination with Agilent microarrays and with Significance Analysis of Microarrays statistical test. DEGs were tested as a tumor risk classifier with a machine learning Random Forest algorithm run with gene expression data from all TCGA-PRAD (prostate adenocarcinoma) tumors as input. ChIP-qPCR was performed for histone marks at the promoter of one DEG. Results We show that PVT1 knockdown in androgen-stimulated LNCaP cells caused statistically significant expression upregulation/downregulation of hundreds of genes. Interestingly, PVT1 knockdown caused upregulation of 160 genes that were repressed by androgen, including a significantly enriched set of tumor suppressor genes, and among them FAS, NOV/CCN3, BMF, HRK, IFIT2, AJUBA, DRAIC and TNFRSF21. A 121-gene-set (out of the 160) was able to correctly predict the classification of all 293 intermediate- and high-risk TCGA-PRAD tumors, with a mean ROC area under the curve AUC = 0.89 ± 0.04, pointing to the relevance of these genes in cancer aggressiveness. Native RIP-qPCR in LNCaP showed that PVT1 was associated with EZH2, a component of PRC2. PVT1 knockdown followed by ChIP-qPCR showed significant epigenetic remodeling at the enhancer and promoter regions of tumor suppressor gene NOV, one of the androgen-repressed genes that were upregulated upon PVT1 silencing. Conclusions Overall, we provide first evidence that PVT1 was involved in signaling a genome-wide androgen-dependent transcriptional repressive program of tumor suppressor protein-coding genes in prostate cancer cells. Identification of transcriptional inhibition of tumor suppressor genes by PVT1 highlights the pathway to the investigation of mechanisms that lie behind the oncogenic role of PVT1 in cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Interestingly, lncPVT1 is described as a chromatin modifier [71]. It has been demonstrated to bind the histone methyltransferase Enhancer of Zeste Homolog-2 (EZH2), a catalytic subunit of polycomb-repressive complex 2 (PRC2), leading to the direct histone methylation of several gene promoters, including the angiopoietin-like 4 (ANGPTL4) in cholangiocarcinoma [70] and trophoblast cells [72], the thyroidstimulating hormone receptor (TSHR) in thyroid carcinoma [73], the forkhead box f1 (FOXF1) in breast cancer [74], the large tumour suppressor kinase 2 (LATS2) in non-small-cell lung cancer (NSCLC) [49], the tumour suppressors p15 and p16 in GC [66], the miR-146a in prostate cancer [75], the miR-200c in melanoma [76], and the miR-200b in cervical cancer [77]. lncPVT1 could also recruit DNMT1 via EZH2 and promote DNA methylation of the miR-18b-5p promoter in gallbladder cancer (GBC) [68].…”

Section: Two Molecules Same Function?mentioning

confidence: 99%

Unravelling similarities and differences in the role of circular and linear PVT1 in cancer and human disease

et al. 2021

View full text Add to dashboard Cite

The plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNA gene involved in human disease, mainly in cancer onset/progression. Although widely analysed, its biological roles need to be further clarified. Notably, functional studies on PVT1 are complicated by the occurrence of multiple transcript variants, linear and circular, which generate technical issues in the experimental procedures used to evaluate its impact on human disease. Among the many PVT1 transcripts, the linear PVT1 (lncPVT1) and the circular hsa_circ_0001821 (circPVT1) are frequently reported to perform similar pathologic and pro-tumorigenic functions when overexpressed. The stimulation of cell proliferation, invasion and drug resistance, cell metabolism regulation, and apoptosis inhibition is controlled through multiple targets, including MYC, p21, STAT3, vimentin, cadherins, the PI3K/AKT, HK2, BCL2, and CASP3. However, some of this evidence may originate from an incorrect evaluation of these transcripts as two separate molecules, as they share the lncPVT1 exon-2 sequence. We here summarise lncPVT1/circPVT1 functions by mainly focusing on shared pathways, pointing out the potential bias that may exist when the biological role of each transcript is analysed. These considerations may improve the knowledge about lncPVT1/circPVT1 and their specific targets, which deserve further studies due to their diagnostic, prognostic, and therapeutic potential.

show abstract

“…Another example is PVT1, which acts as an oncogenic lncRNA in cancers, including BC. Guo et al showed that PVT1 inhibits the expression of the tumor suppressor gene FOXF1 by recruiting EZH2, a catalytic subunit of the PRC2 complex, consequently, increasing H3K27me3 levels in BC ( Guo et al, 2018 ). Last but not least, coming into interactions with chromatin-modifying enzymes not only serves scaffolding and recruitment functions but also may lead to degradation of the proteins and their complexes, as is the case in ANCR, which affects EZH2 stability and inhibits epithelial-mesenchymal transition (EMT), invasion, tumorigenesis and distant metastasis in BC ( Li Z. et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of Long Noncoding RNAs in Breast Cancer Epigenetics and Epitranscriptomics

Wanowska

Samorowska

Szcześniak

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Breast carcinogenesis is a multistep process that involves both genetic and epigenetic changes. Epigenetics refers to reversible changes in gene expression that are not accompanied by changes in gene sequence. In breast cancer (BC), dysregulated epigenetic changes, such as DNA methylation and histone modifications, are accompanied by epitranscriptomic changes, in particular adenine to inosine modifications within RNA molecules. Factors that trigger these phenomena are largely unknown, but there is evidence for widespread participation of long noncoding RNAs (lncRNAs) that already have been linked to virtually any aspect of BC biology, making them promising biomarkers and therapeutic targets in BC patients. Here, we provide a systematic review of known and possible roles of lncRNAs in epigenetic and epitranscriptomic processes, along with methods and tools to study them, followed by a brief overview of current challenges regarding the use of lncRNAs in medical applications.

show abstract

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

Abstract: Plasmacytoma variant translocation 1 (PVT1) expression was elevated in breast cancer tissues and correlated to breast cancer progression and prognosis.

Cited by 6 publications

References 30 publications

PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors

PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors

Unravelling similarities and differences in the role of circular and linear PVT1 in cancer and human disease

Emerging Roles of Long Noncoding RNAs in Breast Cancer Epigenetics and Epitranscriptomics

Contact Info

Product

Resources

About