Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2

Redis, Roxana S.; Vela, Luz E.; Lu, Weiqin; Oliveira, José Farias de; Ivan, Cristina; Rodríguez-Aguayo, Cristian; Adamóski, Douglas; Pasculli, Barbara; Taguchi, Ayumu; Chen, Yunyun; Fernández, Agustín F.; Valledor, Luís; Roosbroeck, Katrien Van; Chang, Samuel F.; Shah, Maitri; Kinnebrew, Garrett; Han, Leng; Atlasi, Yaser; Cheung, Lawrence H.; Huang, Gary B.; Monroig, Paloma del C.; Ramirez, Marc S.; Ivković, Tina Catela; Van, Long; Ling, Hui; Gafà, Roberta; Kapitanović, Sanja; Lanza, Giovanni; Bankson, James A.; Huang, Peng; Lai, Stephen Y.; Bast, Robert C.; Rosenblum, Michael G.; Radovich, Milan; Ivan, Mircea; Bartholomeusz, Geoffrey; Liang, Han; Fraga, Mario F.; Widger, William R.; Hanash, Samir M.; Berindan‐Neagoe, Ioana; López-Berestein, Gabriel; Dias, Sandra M.G.; Calin, George A.

doi:10.1016/j.molcel.2016.02.006

Cited by 44 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported the allele-specific functionality of CCAT2 in colon cancer. The CCAT2 G and T alleles differentially modulate cellular metabolism by regulating the alternative splicing of GLS to preferentially induce the expression of GAC, the oncogenic isoform of GLS (Redis et al 2016). This is further supported by our data that both the G and T alleles can spontaneously initiate stable MDS/MPN phenotype in mice.…”

Section: Ccat2 Induces Myeloid Malignanciessupporting

confidence: 81%

“…The antibodies used for the analyses are listed in Supplemental Table S1A. RNA pulldown and RNA immunoprecipitation experiments were performed on CCAT2-overexpressing cell lines as previously described (Redis et al 2016). For EZH2 protein stability analysis, cellular protein degradation was monitored after blockage of de novo protein synthesis via cycloheximide treatment.…”

Section: Ezh2 Expression Analysismentioning

confidence: 99%

“…Variation in this single nucleotide results in an altered secondary structure of the RNA at the SNP locus, accounting for the distinct functional roles of the two RNAs. In colon cancer, CCAT2 alleles can bind the two subunits of the Cleavage Factor I (CFIm) complex with distinct affinities, thus regulating the alternative splicing of glutaminase (GLS) and consequently reprogramming glutamine metabolism (Redis et al 2016). CCAT2 transcript is overexpressed in microsatellite-stable (MSS) colon cancer, breast cancer, gastric cancer, esophageal squamous cell carcinoma and non-small cell lung adenocarcinomas (Ling et al 2013;Redis et al 2013;Qiu et al 2014;Cai et al 2015;Wang et al 2015a,b;Zhang et al 2015) and was shown to induce chromosomal instability and metastases in colon cancer by increasing MYC expression (Ling et al 2013).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cancer-associated rs6983267 SNP and its accompanying long noncoding RNACCAT2induce myeloid malignancies via unique SNP-specific RNA mutations

et al. 2018

Self Cite

View full text Add to dashboard Cite

The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific transgenic mice, we demonstrate that overexpression leads to spontaneous myeloid malignancies. We further identified that is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and in myeloid malignancies.

show abstract

Section: Ccat2 Induces Myeloid Malignanciessupporting

confidence: 81%

Section: Ezh2 Expression Analysismentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Cancer-associated rs6983267 SNP and its accompanying long noncoding RNACCAT2induce myeloid malignancies via unique SNP-specific RNA mutations

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent studies confirmed that the lncRNA CCAT2, located at the 8q24 amplicon of the cancer risk-associated rs6983267 SNP, regulated the cancer metabolism in vitro and in vivo by directly interacting in an allele-specific manner with a protein complex (15,16). The chromosomal region 8q24 emerged as an important region for genetic susceptibility in various cancer types, thus DNA methylation or SNPs at this locus may contribute to cancer risk (17,18).…”

Section: Discussionmentioning

confidence: 95%

Effect of silencing colon cancer-associated transcript 2 on the proliferation, apoptosis and autophagy of gastric cancer BGC-823 cells

Lee

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

The role of long non-coding RNAs (lncRNAs) in the carcinogenesis and progression of tumors has been receiving increasing attention. Colon cancer-associated transcript 2 (CCAT2), a type of oncogenic lncRNA, is regarded as a novel biomarker of poor prognosis and metastasis in various types of cancer. However, the molecular contributions of CCAT2 to gastric cancer (GC) progression remain largely unclear. The aim of the present study was to demonstrate the effect of silencing CCAT2 on the biological behavior of GC BGC-823 cells and illustrate the potential underlying molecular mechanisms. A short hairpin RNA interference plasmid pRNAT-U6.1-CCAT2 targeting CCAT2 was successfully constructed. At 48 h after transfection with the interference plasmid, the survival rate of BGC-823 cells was significantly decreased, as determined by the MTT assay. In addition, RT-qPCR results revealed that CCAT2 gene expression was effectively suppressed by the transfection, while POU domain class 5 transcription factor 1B (POU5F1B) gene expression was significantly decreased. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay further revealed that the apoptotic index was significantly higher in the interference group. Western blot analysis also demonstrated that the expression of beclin-1 protein was significantly increased, whereas the expression levels of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) proteins were downregulated in the interference group. In conclusion, CCAT2 was able to positively regulate the expression of POU5F1B gene. Furthermore, silencing of CCAT2 gene inhibited the proliferation of BGC-823 cells, as well as induced apoptosis and autophagy in BGC-823 cells, by suppression of the PI3K/mTOR signaling pathways.

show abstract

“…45,46 CCAT2 has been demonstrated to regulate glutamine metabolism in an allele-specific manner. 47 The CCAT2 alleles interact with the cleavage factor I (CFIm) complex with distinct affinities to regulate the alternative splicing of GLS. Briefly, the CCAT2 G allele promotes the production of GAC (glutaminase isoform C), a GLS isoform with higher catalytic activity, to supply the production of more glutamate for the TCA cycle.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNAs in the metabolic control of inflammation and immune disorders

Cao

2018

Cell Mol Immunol

View full text Add to dashboard Cite

The metabolic control of immune cell development and function has been shown to be critical for the maintenance of immune homeostasis and is also involved in the pathogenesis of immune disorders. Pathogenic infections or cancers may induce metabolic reprogramming through different pathways to meet the energy and metabolite demands for pathogen propagation or cancer progression. In addition, some deregulated metabolites could trigger or regulate immune responses, thus causing chronic inflammation or immune disorders, such as viral infection, cancer and obesity. Therefore, the methods through which metabolism is regulated and the role of metabolic regulation in inflammation and immunity attract much attention. Epigenetic regulation of inflammation and immunity is an emerging field. Long noncoding RNAs (lncRNAs) have been well documented to play crucial roles in many biological processes through diverse mechanisms, including immune regulation and metabolic alternation. Here, we review the functions and mechanisms of lncRNAs in the metabolic regulation of inflammatory immune disorders, aiming to deepen our understanding of the epigenetic regulation of inflammation and immunity.

show abstract

Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2

Cited by 44 publications

References 0 publications

Cancer-associated rs6983267 SNP and its accompanying long noncoding RNACCAT2induce myeloid malignancies via unique SNP-specific RNA mutations

Cancer-associated rs6983267 SNP and its accompanying long noncoding RNACCAT2induce myeloid malignancies via unique SNP-specific RNA mutations

Effect of silencing colon cancer-associated transcript 2 on the proliferation, apoptosis and autophagy of gastric cancer BGC-823 cells

Long noncoding RNAs in the metabolic control of inflammation and immune disorders

Contact Info

Product

Resources

About