Low DICER1 expression is associated with attenuated neutrophil differentiation and autophagy of NB4 APL cells

Wampfler, Julian; Federzoni, Elena; Torbett, Bruce E; Fey, Martin; Tschan, Mario (2015). Low DICER1 expression is associated with attenuated neutrophil differentiation and autophagy of NB4 APL cells. Journal of leukocyte biology, 98(3), pp. 357-363. Society for Leukocyte Biology 10.1189/jlb.1AB0514-258R

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Successful myeloid differentiation depends on the expression of a series of miRNAs. Thus, it is hardly surprising that miRNAs are globally repressed in AML, a disease mainly characterized by a block in cellular myeloid differentiation. Studies investigating the mechanisms for low miRNA expression in AML has mostly focused on altered transcriptional regulation or deletions, whereas defective miRNA processing has received less attention. In this study, we report that the expression of the key miRNA processing enzyme DICER1 is down-regulated in primary AML patient samples and healthy CD34(+) progenitor cells as compared with granulocytes. In line with these findings, Dicer1 expression was induced significantly in AML cell lines upon neutrophil differentiation. The knocking down of DICER1 in AML cells significantly attenuated neutrophil differentiation, which was paralleled by decreased expression of miRNAs involved in this process. Moreover, we found that inhibiting DICER1 attenuated the activation of autophagy, a cellular recycling process that is needed for proper neutrophil differentiation of AML cells. Our results clearly indicate that DICER1 plays a novel role in neutrophil differentiation as well as in myeloid autophagy of AML cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Med. Onkologie / Hämatologie (Erw.)

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Wampfler, Julian; Federzoni, Elena; Fey, Martin and Tschan, Mario

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0741-5400

Publisher:

Society for Leukocyte Biology

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

14 Jul 2015 14:13

Last Modified:

11 May 2016 11:56

Publisher DOI:

10.1189/jlb.1AB0514-258R

PubMed ID:

25990244

Uncontrolled Keywords:

AML, RNAi, processing machinery

BORIS DOI:

10.7892/boris.70315

URI:

https://boris.unibe.ch/id/eprint/70315

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