Abstract 3997: MiR-181 promotes megakaryocyte differentiation

Abstract

Abstract MiRNAs have attracted attention due to their key regulatory functions in biological events such as proliferation, differentiation, apoptosis, and tumorigenesis. A few recent studies reported on the existence of a reciprocal regulatory loop between the family of let-7 miRNAs and an RNA-binding protein lin28, both of which play important roles during cell differentiation. Using bipotent K562 human leukemia cells and human CD34+ hematopoietic stem cells as research models, we demonstrate that let-7 and lin28 appear to exhibit inverse expression trends in phorbol ester-induced megakaryocyte differentiation, while miR-181 is up-regulated early during this process. Enforced expression of miR-181a in K562 cells effectively represses lin28 expression, breaking up the lin28-let-7 reciprocal regulatory loop, and sequentially triggers megakaryocyte differentiation as measured by CD41 and CD61 induction. Elevated miR-181 also significantly increases the number of megakaryocyte colonies in CD34+ hematopoietic stem cells. However, miR-181 expression levels only slightly change during hemin-induced erythrocyte differentiation. These results suggest that miR-181 can function as a “molecular switch” during hematopoietic lineage differentiation and can be a potential target for future miRNA-oriented therapeutics for human cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3997. doi:10.1158/1538-7445.AM2011-3997