TY  - JOUR
A1  - Uebbing, Stella
A1  - Kreiß, Marius
A1  - Scholl, Friederike
A1  - Häfner, Ann‐Kathrin
A1  - Sürün, Duran
A1  - Garscha, Ulrike
A1  - Werz, Oliver
A1  - Basavarajappa, Devaraj
A1  - Samuelsson, Bengt
A1  - Rådmark, Olof
A1  - Süß, Beatrix
A1  - Steinhilber, Dieter
T1  - Modulation of microRNA processing by 5-lipoxygenase
T2  - The FASEB journal
N2  - The miRNA biogenesis is tightly regulated to avoid dysfunction and consequent disease development. Here, we describe modulation of miRNA processing as a novel noncanonical function of the 5-lipoxygenase (5-LO) enzyme in monocytic cells. In differentiated Mono Mac 6 (MM6) cells, we found an in situ interaction of 5-LO with Dicer, a key enzyme in miRNA biogenesis. RNA sequencing of small noncoding RNAs revealed a functional impact, knockout of 5-LO altered the expression profile of several miRNAs. Effects of 5-LO could be observed at two levels. qPCR analyses thus indicated that (a) 5-LO promotes the transcription of the evolutionarily conserved miR-99b/let-7e/miR-125a cluster and (b) the 5-LO-Dicer interaction downregulates the processing of pre-let-7e, resulting in an increase in miR-125a and miR-99b levels by 5-LO without concomitant changes in let-7e levels in differentiated MM6 cells. Our observations suggest that 5-LO regulates the miRNA profile by modulating the Dicer-mediated processing of distinct pre-miRNAs. 5-LO inhibits the formation of let-7e which is a well-known inducer of cell differentiation, but promotes the generation of miR-99b and miR-125a known to induce cell proliferation and the maintenance of leukemic stem cell functions.
KW  - cancer
KW  - Dicer
KW  - inflammation
KW  - leukotriene
KW  - miRNA
KW  - 5-lipoxygenase
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56510
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-565102
SN  - 1530-6860
SN  - 0892-6638
VL  - 2020
PB  - Wiley
CY  - Hoboken, NJ
ER  -