Modulation of microRNA processing by 5-lipoxygenase
Here, we describe the 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 non-coding RNAs revealed a functional impact, knockout of 5-LO altered the expression profile of several miRNAs. 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 induces cell differentiation and promotes the generation of the oncomirs miR-99b and miR-125a which induce cell proliferation and the maintenance of leukemic stem cell functions. Overall design: Small RNA profiling of differentiated Mono Mac 6 (ACC 124) wild type (WT) and 5-Lipoxygenase knockout (5-LO KO) cells