TY - JOUR
T1 - The novel lncRNA BlackMamba controls the neoplastic phenotype of ALK− anaplastic large cell lymphoma by regulating the DNA helicase HELLS
AU - Fragliasso, Valentina
AU - Verma, Akanksha
AU - Manzotti, Gloria
AU - Tameni, Annalisa
AU - Bareja, Rohan
AU - Heavican, Tayla B.
AU - Iqbal, Javeed
AU - Wang, Rui
AU - Fiore, Danilo
AU - Mularoni, Valentina
AU - Chan, Wing C.
AU - Lhoumaud, Priscillia
AU - Skok, Jane
AU - Zanetti, Eleonora
AU - Merli, Francesco
AU - Ciarrocchi, Alessia
AU - Elemento, Oliver
AU - Inghirami, Giorgio
N1 - Funding Information:
Acknowledgements We thank Dr Alan Epstein, who provided the TLBR-1 and 2 cells lines. We also thank Marina Grassi for technical help and Jacqueline Costa for English editing. This work was funded by the Italian Association for Cancer Research Special Program in Clinical Molecular Oncology, Milan (5 × 1000 No. 10007, GI), 7011-16 SCOR grant from the Leukemia & Lymphoma Society/SCOR grant (GI), by the Ministero della Salute (Ricerca Finalizzata No. GR-2016-02364298, VF), and R35GM122515 (JS). We thank the Epigenetic Core at Weill Cornell Medicine and the Genome Technology Center at New York University and GRADE Onlus Foundation.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - The molecular mechanisms leading to the transformation of anaplastic lymphoma kinase negative (ALK−) anaplastic large cell lymphoma (ALCL) have been only in part elucidated. To identify new culprits which promote and drive ALCL, we performed a total transcriptome sequencing and discovered 1208 previously unknown intergenic long noncoding RNAs (lncRNAs), including 18 lncRNAs preferentially expressed in ALCL. We selected an unknown lncRNA, BlackMamba, with an ALK− ALCL preferential expression, for molecular and functional studies. BlackMamba is a chromatin-associated lncRNA regulated by STAT3 via a canonical transcriptional signaling pathway. Knockdown experiments demonstrated that BlackMamba contributes to the pathogenesis of ALCL regulating cell growth and cell morphology. Mechanistically, BlackMamba interacts with the DNA helicase HELLS controlling its recruitment to the promoter regions of cell-architecture-related genes, fostering their expression. Collectively, these findings provide evidence of a previously unknown tumorigenic role of STAT3 via a lncRNA-DNA helicase axis and reveal an undiscovered role for lncRNA in the maintenance of the neoplastic phenotype of ALK−ALCL.
AB - The molecular mechanisms leading to the transformation of anaplastic lymphoma kinase negative (ALK−) anaplastic large cell lymphoma (ALCL) have been only in part elucidated. To identify new culprits which promote and drive ALCL, we performed a total transcriptome sequencing and discovered 1208 previously unknown intergenic long noncoding RNAs (lncRNAs), including 18 lncRNAs preferentially expressed in ALCL. We selected an unknown lncRNA, BlackMamba, with an ALK− ALCL preferential expression, for molecular and functional studies. BlackMamba is a chromatin-associated lncRNA regulated by STAT3 via a canonical transcriptional signaling pathway. Knockdown experiments demonstrated that BlackMamba contributes to the pathogenesis of ALCL regulating cell growth and cell morphology. Mechanistically, BlackMamba interacts with the DNA helicase HELLS controlling its recruitment to the promoter regions of cell-architecture-related genes, fostering their expression. Collectively, these findings provide evidence of a previously unknown tumorigenic role of STAT3 via a lncRNA-DNA helicase axis and reveal an undiscovered role for lncRNA in the maintenance of the neoplastic phenotype of ALK−ALCL.
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U2 - 10.1038/s41375-020-0754-8
DO - 10.1038/s41375-020-0754-8
M3 - Article
C2 - 32123306
AN - SCOPUS:85081265261
SN - 0887-6924
VL - 34
SP - 2964
EP - 2980
JO - Leukemia
JF - Leukemia
IS - 11
ER -