title: Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2.
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.
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Roxana S
authors: RS
authors: Redis
authors: Department of Biology & Biochemistry, University of Houston, Houston, TX 77204, USA.
authors: Luz E
authors: LE
authors: Vela
authors: 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.
authors: Weiqin
authors: W
authors: Lu
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas 13083-100, Brazil.
authors: Juliana
authors: J
authors: Ferreira de Oliveira
authors: Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Cristina
authors: C
authors: Ivan
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Cristian
authors: C
authors: Rodriguez-Aguayo
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas 13083-100, Brazil.
authors: Douglas
authors: D
authors: Adamoski
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Barbara
authors: B
authors: Pasculli
authors: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Ayumu
authors: A
authors: Taguchi
authors: Department of Head & Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Yunyun
authors: Y
authors: Chen
authors: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain.
authors: Agustin F
authors: AF
authors: Fernandez
authors: Department of Organisms and Systems Biology, University of Oviedo, Ovideo 33006, Spain.
authors: Luis
authors: L
authors: Valledor
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Katrien
authors: K
authors: Van Roosbroeck
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Samuel
authors: S
authors: Chang
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Maitri
authors: M
authors: Shah
authors: Department of Surgery, Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Garrett
authors: G
authors: Kinnebrew
authors: Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.
authors: Leng
authors: L
authors: Han
authors: Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam 3015, the Netherlands.
authors: Yaser
authors: Y
authors: Atlasi
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Lawrence H
authors: LH
authors: Cheung
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Gilbert Y
authors: GY
authors: Huang
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Paloma
authors: P
authors: Monroig
authors: Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Marc S
authors: MS
authors: Ramirez
authors: 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.
authors: Tina
authors: T
authors: Catela Ivkovic
authors: Department of Biology & Biochemistry, University of Houston, Houston, TX 77204, USA.
authors: Long
authors: L
authors: Van
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Hui
authors: H
authors: Ling
authors: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara 44121, Italy.
authors: Roberta
authors: R
authors: Gafà
authors: Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb 10000, Croatia.
authors: Sanja
authors: S
authors: Kapitanovic
authors: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara 44121, Italy.
authors: Giovanni
authors: G
authors: Lanza
authors: Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: James A
authors: JA
authors: Bankson
authors: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Peng
authors: P
authors: Huang
authors: Department of Head & Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Stephen Y
authors: SY
authors: Lai
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Robert C
authors: RC
authors: Bast
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Michael G
authors: MG
authors: Rosenblum
authors: Department of Surgery, Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Milan
authors: M
authors: Radovich
authors: Department of Medicine, Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Mircea
authors: M
authors: Ivan
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Geoffrey
authors: G
authors: Bartholomeusz
authors: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Han
authors: H
authors: Liang
authors: Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Asturias 33424, Spain.
authors: Mario F
authors: MF
authors: Fraga
authors: Department of Biology & Biochemistry, University of Houston, Houston, TX 77204, USA.
authors: William R
authors: WR
authors: Widger
authors: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Samir
authors: S
authors: Hanash
authors: 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.
authors: Ioana
authors: I
authors: Berindan-Neagoe
authors: 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.
authors: Gabriel
authors: G
authors: Lopez-Berestein
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas 13083-100, Brazil.
authors: Andre L B
authors: ALB
authors: Ambrosio
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas 13083-100, Brazil.
authors: Sandra M
authors: SM
authors: Gomes Dias
authors: 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: gcalin@mdanderson.org.
authors: George A
authors: GA
authors: Calin
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D004734:Energy Metabolism; D005972:Glutaminase / Q000235:genetics*; D045325:HCT116 Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: D012322:RNA Precursors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C450562:cleavage factor Im, human; C000609264:long non-coding RNA CCAT2, human; D039221:mRNA Cleavage and Polyadenylation Factors; D005972:Glutaminase