The novel lncRNA BlackMamba controls the neoplastic phenotype of ALK- anaplastic large cell lymphoma by regulating the DNA helicase HELLS
| Autor: | Tayla Heavican, Javeed Iqbal, Eleonora Zanetti, Valentina Mularoni, Valentina Fragliasso, Gloria Manzotti, Rohan Bareja, Danilo Fiore, Wing C. Chan, Annalisa Tameni, Akanksha Verma, Rui Wang, Olivier Elemento, Jane A. Skok, Priscillia Lhoumaud, Giorgio Inghirami, Alessia Ciarrocchi, Francesco Merli |
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| Přispěvatelé: | Fragliasso, V., Verma, A., Manzotti, G., Tameni, A., Bareja, R., Heavican, T. B., Iqbal, J., Wang, R., Fiore, D., Mularoni, V., Chan, W. C., Lhoumaud, P., Skok, J., Zanetti, E., Merli, F., Ciarrocchi, A., Elemento, O., Inghirami, G. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Biopsy Biology DNA Helicase Cell morphology Models Biological HELLS Clonal Evolution 03 medical and health sciences ALCL LncRNAs 0302 clinical medicine RNA interference Cell Line Tumor hemic and lymphatic diseases medicine Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Gene Silencing Promoter Regions Genetic Gene Anaplastic large-cell lymphoma Cell Proliferation Regulation of gene expression Gene Expression Profiling MicroRNA Hematology medicine.disease Phenotype Gene Expression Regulation Neoplastic 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Lymphoma Large-Cell Anaplastic RNA Interference RNA Long Noncoding Human |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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