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

Autor(es):Mostrar menos -

Redis, Roxana S. ^[1] ; Vela, Luz E. ^[2] ; Lu, Weiqin ^{[3, 4]} ; de Oliveira, Juliana Ferreira ^[5] ; Ivan, Cristina ^[6] ; Rodriguez-Aguayo, Cristian ^[1] ; Adamoski, Douglas ^[5] ; Pasculli, Barbara ^[1] ; Taguchi, Ayumu ^[4] ; Chen, Yunyun ^[7] ; Fernandez, Agustin F. ^[8] ; Valledor, Luis ^[9] ; Van Roosbroeck, Katrien ^[1] ; Chang, Samuel ^[1] ; Shah, Maitri ^[1] ; Kinnebrew, Garrett ^[10] ; Han, Leng ^[11] ; Atlasi, Yaser ^{[12, 13]} ; Cheung, Lawrence H. ^[1] ; Huang, Gilbert Y. ^[1] ; Monroig, Paloma ^[1] ; Ramirez, Marc S. ^[14] ; Ivkovic, Tina Catela ^{[1, 15]} ; Van, Long ; Ling, Hui ^[1] ; Gafa, Roberta ^[16] ; Kapitanovic, Sanja ^[15] ; Lanza, Giovanni ^[16] ; Bankson, James A. ^[14] ; Huang, Peng ^[4] ; Lai, Stephen Y. ^[7] ; Bast, Robert C. ^[1] ; Rosenblum, Michael G. ^[1] ; Radovich, Milan ^[10] ; Ivan, Mircea ^[17] ; Bartholomeusz, Geoffrey ^[1] ; Liang, Han ^[18] ; Fraga, Mario F. ^[19] ; Widger, William R. ^[20] ; Hanash, Samir ^[21] ; Berindan-Neagoe, Ioana ^{[1, 22, 23]} ; Lopez-Berestein, Gabriel ^{[1, 6]} ; Ambrosio, Andre L. B. ^[5] ; Gomes Dias, Sandra M. ^[5] ; Calin, George A. ^{[1, 6]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 - USA

^[2] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 - USA

^[3] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 - USA

^[4] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 - USA

^[5] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, BR-13083100 Campinas, SP - Brazil

^[6] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Houston, TX 77030 - USA

^[7] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 - USA

^[8] Univ Oviedo, Inst Oncol Asturias IUOPA, HUCA, Canc Epigenet Lab, E-33006 Oviedo - Spain

^[9] Univ Oviedo, Dept Organisms & Syst Biol, Oviedo 33006 - Spain

^[10] Indiana Univ Sch Med, Dept Surg Med & Mol Genet, Indianapolis, IN 46202 - USA

^[11] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, McGovern Med Sch, Houston, TX 77030 - USA

^[12] Erasmus MC, Josephine Nefkens Inst, Dept Pathol, NL-3015 Rotterdam - Netherlands

^[13] Radboud Inst Mol Life Sci, Dept Mol Biol, NL-6525 Nijmegen - Netherlands

^[14] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Div Diagnost Imaging, Houston, TX 77030 - USA

^[15] Rudjer Boskovic Inst, Lab Personalized Med, Div Mol Med, POB 1016, Zagreb 10000 - Croatia

^[16] Univ Ferrara, Dept Morphol Surg & Expt Med, I-44121 Ferrara - Italy

^[17] Indiana Univ Sch Med, Dept Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 - USA

^[18] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 - USA

^[19] CINN CSIC, Nanomat & Nanotechnol Res Ctr, Asturias 33424 - Spain

^[20] Long Van, Univ Houston, Dept Biol & Biochem, Houston, TX 77204 - USA

^[21] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 - USA

^[22] Univ Med & Pharm Iuliu Hatieganu, Res Ctr Funct Genom Biomed & Translat Med, Cluj Napoca 400012 - Romania

^[23] Inst Oncol, Dept Funct Genom, Cluj Napoca 400015 - Romania

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR CELL; v. 61, n. 4, p. 520-534, FEB 18 2016.
• Citações Web of Science: 63

Resumo

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. (AU)

• Processo FAPESP: 14/17820-3 - Regulação pós-transcricional da enzima glutaminase por HuR e sua relação com os altos níveis glutaminolíticos tumorais
• Beneficiário: Douglas Adamoski Meira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 14/20673-2 - Estudos biofísicos e bioquímicos do complexo carreador de piruvato mitocondrial e da enzima glutaminase em complexo com novos parceiros
• Beneficiário: Andre Luis Berteli Ambrosio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/15968-3 - Entendimento da regulação funcional da enzima glutaminase e desenvolvimento de inibidores como terapia de combate ao câncer
• Beneficiário: Sandra Martha Gomes Dias
• Modalidade de apoio: Auxílio à Pesquisa - Regular