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A therapeutically targetable positive feedback loop between lnc-HLX-2-7, HLX, and MYC that promotes group 3 medulloblastoma.
Katsushima, Keisuke; Joshi, Kandarp; Yuan, Menglang; Romero, Brigette; Batish, Mona; Stapleton, Stacie; Jallo, George; Kolanthai, Elayaraja; Seal, Sudipta; Saulnier, Olivier; Taylor, Michael D; Wechsler-Reya, Robert J; Eberhart, Charles G; Perera, Ranjan J.
Afiliação
  • Katsushima K; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD 21231, USA; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA.
  • Joshi K; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD 21231, USA; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA.
  • Yuan M; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD 21231, USA; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA.
  • Romero B; Department of Medical and Molecular Sciences, University of Delaware, 15 Innovation Way, Newark, DE 19701, USA.
  • Batish M; Department of Medical and Molecular Sciences, University of Delaware, 15 Innovation Way, Newark, DE 19701, USA.
  • Stapleton S; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA.
  • Jallo G; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA.
  • Kolanthai E; Advanced Materials Processing and Analysis Center, Nanoscience and Technology Center, Materials Science and Engineering, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
  • Seal S; Advanced Materials Processing and Analysis Center, Nanoscience and Technology Center, Materials Science and Engineering, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
  • Saulnier O; Genomics and Development of Childhood Cancers, Institut Curie, PSL University, 75005 Paris, France; INSERM U830, Cancer Heterogeneity Instability and Plasticity, Institut Curie, PSL University, 75005 Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with
  • Taylor MD; Texas Children's Cancer Center, Hematology-Oncology Section, Houston, TX 77004, USA; Department of Pediatrics - Hematology/Oncology and Neurosurgery, Baylor College of Medicine, Houston, TX 77004, USA.
  • Wechsler-Reya RJ; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  • Eberhart CG; Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross Bldg. 558, Baltimore, MD 21205, USA.
  • Perera RJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD 21231, USA; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA. Electronic address: jperera2@jh.edu.
Cell Rep ; 43(3): 113938, 2024 Mar 26.
Article em En | MEDLINE | ID: mdl-38460130
ABSTRACT
Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-lnc-HLX-2-7) inhibits tumor growth by 40%-50% in an intracranial MB xenograft mouse model. Combining CNP-lnc-HLX-2-7 with standard-of-care cisplatin further inhibits tumor growth and significantly prolongs mouse survival compared with CNP-lnc-HLX-2-7 monotherapy. Thus, the lnc-HLX-2-7-HLX-MYC axis is important for regulating G3 MB progression, providing a strong rationale for using lnc-HLX-2-7 as a therapeutic target for G3 MBs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / RNA Longo não Codificante / Meduloblastoma Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / RNA Longo não Codificante / Meduloblastoma Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos