title: Oncogenic Role of Fusion-circRNAs Derived from Cancer-Associated Chromosomal Translocations.
abstract: Chromosomal translocations encode oncogenic fusion proteins that have been proven to be causally involved in tumorigenesis. Our understanding of whether such genomic alterations also affect non-coding RNAs is limited, and their impact on circular RNAs (circRNAs) has not been explored. Here, we show that well-established cancer-associated chromosomal translocations give rise to fusion circRNAs (f-circRNA) that are produced from transcribed exons of distinct genes affected by the translocations. F-circRNAs contribute to cellular transformation, promote cell viability and resistance upon therapy, and have tumor-promoting properties in in vivo models. Our work expands the current knowledge regarding molecular mechanisms involved in cancer onset and progression, with potential diagnostic and therapeutic implications.
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jlenia
authors.initials: J
authors.lastname: Guarnerio
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Bezzi
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jong Cheol
authors.initials: JC
authors.lastname: Jeong
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Stella V
authors.initials: SV
authors.lastname: Paffenholz
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Berry
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Matteo M
authors.initials: MM
authors.lastname: Naldini
authors.affiliation: Department of Biomedicine and Prevention, University Tor Vergata, and Fondazione Santa Lucia, 00173 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.affiliation: Cancer Science Institute of Singapore and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Tay
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: ppandolf@bidmc.harvard.edu.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012313:RNA / Q000378:metabolism*; D000079962:RNA, Circular; D014178:Translocation, Genetic
chemical_list: C474558:MLL-AF9 fusion protein, human; D015514:Oncogene Proteins, Fusion; D000079962:RNA, Circular; D051788:Myeloid-Lymphoid Leukemia Protein; D012313:RNA