title: RBM5-AS1 Is Critical for Self-Renewal of Colon Cancer Stem-like Cells.
abstract: Cancer-initiating cells (CIC) undergo asymmetric growth patterns that increase phenotypic diversity and drive selection for chemotherapeutic resistance and tumor relapse. WNT signaling is a hallmark of colon CIC, often caused by APC mutations, which enable activation of β-catenin and MYC Accumulating evidence indicates that long noncoding RNAs (lncRNA) contribute to the stem-like character of colon cancer cells. In this study, we report enrichment of the lncRNA RBM5-AS1/LUST during sphere formation of colon CIC. Its silencing impaired WNT signaling, whereas its overexpression enforced WNT signaling, cell growth, and survival in serum-free media. RBM5-AS1 has been little characterized previously, and we determined it to be a nuclear-retained transcript that selectively interacted with β-catenin. Mechanistic investigations showed that silencing or overexpression of RBM5-AS1 caused a respective loss or retention of β-catenin from TCF4 complexes bound to the WNT target genes SGK1, YAP1, and MYC Our work suggests that RBM5-AS1 activity is critical for the functional enablement of colon cancer stem-like cells. Furthermore, it defines the mechanism of action of RBM5-AS1 in the WNT pathway via physical interactions with β-catenin, helping organize transcriptional complexes that sustain colon CIC function. Cancer Res; 76(19); 5615-27. ©2016 AACR.
authors: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York. SEMM, European School of Molecular Medicine, Naples, Italy.
authors: Serena
authors: S
authors: Di Cecilia
authors: Department of Medicine, Division of Nephrology, Bioinformatics Laboratory, Icahn School of Medicine at Mount Sinai, New York.
authors: Fan
authors: F
authors: Zhang
authors: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York.
authors: Ana
authors: A
authors: Sancho
authors: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York.
authors: SiDe
authors: S
authors: Li
authors: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York.
authors: Francesca
authors: F
authors: Aguiló
authors: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York.
authors: Yifei
authors: Y
authors: Sun
authors: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York.
authors: Madhumitha
authors: M
authors: Rengasamy
authors: Department of Medicine, Division of Nephrology, Bioinformatics Laboratory, Icahn School of Medicine at Mount Sinai, New York.
authors: Weijia
authors: W
authors: Zhang
authors: CEINGE-Biotecnologie avanzate, Università degli Studi di Napoli-Federico II, Naples, Italy.
authors: Luigi
authors: L
authors: Del Vecchio
authors: CEINGE-Biotecnologie avanzate, Università degli Studi di Napoli-Federico II, Naples, Italy.
authors: Francesco
authors: F
authors: Salvatore
authors: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York. martin.walsh@mssm.edu.
authors: Martin J
authors: MJ
authors: Walsh
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology; D051927:CD24 Antigen / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D019938:Cyclin D1 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D016259:Genes, myc; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics; D051379:Mice; D014411:Neoplastic Stem Cells / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016372:RNA, Antisense / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051927:CD24 Antigen; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; D000073940:Transcription Factor 4; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D000099184:Serum-Glucocorticoid Regulated Kinases; C473448:RBM5 protein, human; C532096:TCF4 protein, human