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

Mircea Ivan, Long Van, Hui Ling, Roberta Gafà, Sanja Kapitanovic, Giovanni Lanza, James A Bankson, Peng Huang, Stephen Y Lai, Robert C Bast, Michael G Rosenblum, Milan Radovich, Tina Catela Ivkovic, Geoffrey Bartholomeusz, Han Liang, Mario F Fraga, William R Widger, Samir Hanash, Ioana Berindan-Neagoe, Gabriel Lopez-Berestein, Andre L B Ambrosio, Sandra M Gomes Dias, George A Calin, Luis Valledor, Luz E Vela, Weiqin Lu, Juliana Ferreira de Oliveira, Cristina Ivan, Cristian Rodriguez-Aguayo, Douglas Adamoski, Barbara Pasculli, Ayumu Taguchi, Yunyun Chen, Agustin F Fernandez, Roxana S Redis, Katrien Van Roosbroeck, Samuel Chang, Maitri Shah, Garrett Kinnebrew, Leng Han, Yaser Atlasi, Lawrence H Cheung, Gilbert Y Huang, Paloma Monroig, Marc S Ramirez

Journal: Molecular cell 2016;61(4):520-534

PMID: 26853146

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.

Copyright © 2016 Elsevier Inc. All rights reserved.

Address: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Biology & Biochemistry, University of Houston, Houston, TX 77204, USA.; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas 13083-100, Brazil.; Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Head & Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain.; Department of Organisms and Systems Biology, University of Oviedo, Ovideo 33006, Spain.; Department of Surgery, Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.; Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam 3015, the Netherlands.; Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb 10000, Croatia.; Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara 44121, Italy.; Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb 10000, Croatia.; Department of Medicine, Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Asturias 33424, Spain.; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Research Center for Functional Genomics, Biomedicine and Translational Medicine, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca 400012, Romania; Department of Functional Genomics, The Oncology Institute, Cluj-Napoca 400015, Romania.; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: [email protected].
Bant logo

© Copyright 2026, Nutrition Evidence

NED wishes to thank the following organisations for their support:

We use cookies to improve your experience and analyze site traffic with Google Analytics. By continuing to use our site, you agree to our use of cookies. Learn more.