Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allelespecific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68). The CCAT2 interaction with the CFIm complex fine-tunes the alternative splicing of Glutaminase (GLS) by selecting the poly(A) site in intron 14 of the precursor mRNA. These findings uncover a complex, allele-specific regulatory mechanism of cancer metabolism orchestrated by the two alleles of a long ncRNA.

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

GAFA', Roberta;LANZA, Giovanni;
2016

Abstract

Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allelespecific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68). The CCAT2 interaction with the CFIm complex fine-tunes the alternative splicing of Glutaminase (GLS) by selecting the poly(A) site in intron 14 of the precursor mRNA. These findings uncover a complex, allele-specific regulatory mechanism of cancer metabolism orchestrated by the two alleles of a long ncRNA.
2016
Redis, Roxana S.; Vela, Luz E.; Lu, Weiqin; Ferreira de Oliveira, Juliana; Ivan, Cristina; Rodriguez Aguayo, Cristian; Adamoski, Douglas; Pasculli, Barbara; Taguchi, Ayumu; Chen, Yunyun; Fernandez, Agustin F.; Valledor, Luis; Van Roosbroeck, Katrien; Chang, Samuel; Shah, Maitri; Kinnebrew, Garrett; Han, Leng; Atlasi, Yaser; Cheung, Lawrence H.; Huang, Gilbert Y.; Monroig, Paloma; Ramirez, Marc S.; Catela Ivkovic, Tina; Van, Long; Ling, Hui; Gafa', Roberta; Kapitanovic, 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; Berindan Neagoe, Ioana; Lopez Berestein, Gabriel; Ambrosio, Andre L. B.; Gomes Dias, Sandra M.; Calin, George A.
File in questo prodotto:
File Dimensione Formato  
allele specific reprogramming of cancer metabolism by the long non coding RNA CCAT2.pdf

accesso aperto

Descrizione: post print
Tipologia: Post-print
Licenza: Creative commons
Dimensione 1.93 MB
Formato Adobe PDF
1.93 MB Adobe PDF Visualizza/Apri
allele specific reprogramming.Molecular Cell2016.pdf

accesso aperto

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 5.25 MB
Formato Adobe PDF
5.25 MB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2350768
Citazioni
  • ???jsp.display-item.citation.pmc??? 85
  • Scopus 130
  • ???jsp.display-item.citation.isi??? 116
social impact