Long Non-Coding RNAs as Novel Therapeutic Targets in Juvenile Myelomonocytic Leukemia. I
| Autor: | Barbara De Moerloose, Filip Van Nieuwerburgh, Charlotte M. Niemeyer, Pieter Van Vlierberghe, Wouter Van Loocke, Barbara Depreter, Ying Wu, Christian Flotho, Dieter Deforce, Valerie de Haas, Jan Stary, Aurélie Caye, Tim Lammens, Mattias Hofmans, Miriam Erlacher, Hélène Cavé, Jan Philippé |
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| Přispěvatelé: | Clinical sciences, Clinical Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Adolescent Science medicine.medical_treatment Primary Cell Culture Antineoplastic Agents Hematopoietic stem cell transplantation Biology Peripheral blood mononuclear cell Article Transcriptome 03 medical and health sciences 0302 clinical medicine Bone Marrow Medicine and Health Sciences Cancer genomics Tumor Cells Cultured medicine Humans RNA-Seq Child Gene Gene knockdown Multidisciplinary Juvenile myelomonocytic leukemia Gene Expression Regulation Leukemic Infant RNA medicine.disease Healthy Volunteers 030104 developmental biology medicine.anatomical_structure Leukemia Myelomonocytic Juvenile Case-Control Studies Child Preschool Gene Knockdown Techniques 030220 oncology & carcinogenesis Leukocytes Mononuclear Cancer research Medicine Female RNA Long Noncoding Bone marrow Myelodysplastic syndrome |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Scientific Reports SCIENTIFIC REPORTS |
| ISSN: | 2045-2322 |
| Popis: | Juvenile myelomonocytic leukemia (JMML) treatment primarily relies on hematopoietic stem cell transplantation and results in long-term overall survival of 50–60%, demonstrating a need to develop novel treatments. Dysregulation of the non-coding RNA transcriptome has been demonstrated before in this rare and unique disorder of early childhood. In this study, we investigated the therapeutic potential of targeting overexpressed long non-coding RNAs (lncRNAs) in JMML. Total RNA sequencing of bone marrow and peripheral blood mononuclear cell preparations from 19 untreated JMML patients and three healthy children revealed 185 differentially expressed lncRNA genes (131 up- and 54 downregulated). LNA GapmeRs were designed for 10 overexpressed and validated lncRNAs. Molecular knockdown (≥ 70% compared to mock control) after 24 h of incubation was observed with two or more independent GapmeRs in 6 of them. For three lncRNAs (lnc-THADA-4, lnc-ACOT9-1 and NRIR) knockdown resulted in a significant decrease of cell viability after 72 h of incubation in primary cultures of JMML mononuclear cells, respectively. Importantly, the extent of cellular damage correlated with the expression level of the lncRNA of interest. In conclusion, we demonstrated in primary JMML cell cultures that knockdown of overexpressed lncRNAs such as lnc-THADA-4, lnc-ACOT9-1 and NRIR may be a feasible therapeutic strategy. |
| Databáze: | OpenAIRE |
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