| Literature DB >> 26853146 |
Roxana S Redis1, Luz E Vela2, Weiqin Lu3, Juliana Ferreira de Oliveira4, Cristina Ivan5, Cristian Rodriguez-Aguayo1, Douglas Adamoski4, Barbara Pasculli1, Ayumu Taguchi6, Yunyun Chen7, Agustin F Fernandez8, Luis Valledor9, Katrien Van Roosbroeck1, Samuel Chang1, Maitri Shah1, Garrett Kinnebrew10, Leng Han11, Yaser Atlasi12, Lawrence H Cheung1, Gilbert Y Huang1, Paloma Monroig1, Marc S Ramirez13, Tina Catela Ivkovic14, Long Van2, Hui Ling1, Roberta Gafà15, Sanja Kapitanovic16, Giovanni Lanza15, James A Bankson13, Peng Huang6, Stephen Y Lai7, Robert C Bast1, Michael G Rosenblum1, Milan Radovich10, Mircea Ivan17, Geoffrey Bartholomeusz1, Han Liang18, Mario F Fraga19, William R Widger2, Samir Hanash20, Ioana Berindan-Neagoe21, Gabriel Lopez-Berestein22, Andre L B Ambrosio4, Sandra M Gomes Dias4, George A Calin23.
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 allele-specific 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.Entities:
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Year: 2016 PMID： 26853146 PMCID： PMC4982398 DOI： 10.1016/j.molcel.2016.01.015
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970