miR-15a-5p and miR-21-5p contribute to chemoresistance in cytogenetically normal acute myeloid leukaemia by targeting PDCD4, ARL2 and BTG2

Autor: Hélène Schoemans, Lucienne Michaux, Pascale Saussoy, Sandrine Lenglez, Emeline Bollaert, Violaine Havelange, Virginie Vandewalle, Ahmed Essaghir, Carlos Graux, Peter J. M. Valk, Jean-Baptiste Demoulin
Přispěvatelé: UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de biologie hématologique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de thérapie tissulaire et cellulaire, UCL - (MGD) Service d'hématologie, Hematology
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Research & Experimental Medicine
RECOMMENDATIONS
0302 clinical medicine
AML
CHEMOSENSITIVITY
hemic and lymphatic diseases
RNA
Small Interfering
Principal Component Analysis
Cytarabine
apoptosis
Nuclear Proteins
chemoresistance
microRNAs
Leukemia
Myeloid
Acute
Medicine
Research & Experimental
030220 oncology & carcinogenesis
Molecular Medicine
Original Article
Nucleophosmin
Life Sciences & Biomedicine
medicine.drug
medicine.medical_specialty
NPM1
Daunorubicin
Blotting
Western
DIAGNOSIS
03 medical and health sciences
CISPLATIN
Cell Line
Tumor
microRNA
MICRORNA-21 INDUCES RESISTANCE
medicine
MANAGEMENT
Humans
acute myeloid leukaemia
Gene
BTG2
Science & Technology
IDENTIFICATION
business.industry
Cytogenetics
Original Articles
Cell Biology
target genes
030104 developmental biology
Drug Resistance
Neoplasm
Apoptosis
Mutation
CELLS
Cancer research
business
Zdroj: Journal of cellular and molecular medicine, Vol. 25, no. 1, p. 575-585 (2021)
Journal of Cellular and Molecular Medicine
Journal of Cellular and Molecular Medicine, 25(1), 575-585. Wiley-Blackwell Publishing Ltd
ISSN: 1582-1838
Popis: Cytarabine and daunorubicin are old drugs commonly used in the treatment of acute myeloid leukaemia (AML). Refractory or relapsed disease because of chemotherapy resistance is a major issue. microRNAs (miRNAs) were incriminated in resistance. This study aimed to identify miRNAs involved in chemoresistance in AML patients and to define their target genes. We focused on cytogenetically normal AML patients with wild-type NPM1 without FLT3-ITD as the treatment of this subset of patients with intermediate-risk cytogenetics is not well established. We analysed baseline AML samples by small RNA sequencing and compared the profile of chemoresistant to chemosensitive AML patients. Among the miRNAs significantly overexpressed in chemoresistant patients, we revealed miR-15a-5p and miR-21-5p as miRNAs with a major role in chemoresistance in AML. We showed that miR-15a-5p and miR-21-5p overexpression decreased apoptosis induced by cytarabine and/or daunorubicin. PDCD4, ARL2 and BTG2 genes were found to be targeted by miR-15a-5p, as well as PDCD4 and BTG2 by miR-21-5p. Inhibition experiments of the three target genes reproduced the functional effect of both miRNAs on chemosensitivity. Our study demonstrates that miR-15a-5p and miR-21-5p are overexpressed in a subgroup of chemoresistant AML patients. Both miRNAs induce chemoresistance by targeting three pro-apoptotic genes PDCD4, ARL2 and BTG2. ispartof: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE vol:25 issue:1 pages:575-585 ispartof: location:England status: published
Databáze: OpenAIRE
Externí odkaz: