MiR-145 Regulates Hematopoiesis during Zebrafish Development

Abstract

MicroRNA-145 (miR-145) is considered to play key role in many cellular processes, such as proliferation, differentiation and apoptosis by inhibiting target gene expression. The transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression. We are beginning to understand the functions of miRNA-145 played during essential biological processes especially erythropoiesis. Here, we overview the recent findings on miRNA-145 regulation in erythropoiesis development and report the latest advances in understanding their function by unveiling their mRNA targets. Further analysis of miRNA-145 function during erythropoiesis development will allow us to determine the potential for novel miRNA-145-based therapeutic strategies. Haematopoiesis is an active process by which peripheral blood families are developed. It is a process strongly regulated by many essential and unessential factors, including signalling molecules and transcriptional factors. However, the epigenetic regulation of haematopoiesis regulation via microRNAs (miRNAs) remains partially understood. Here, in this study we show that miRNA-145 participates in the haematopoiesis regulation and vascular development of the early stages of erythropoiesis during Zebra fish early developmental stages. Overexpression inhibited the primitive haematopoiesis, characterized by a significant reduced number and limitation of erythropoiesis cells and myeloid expansion significantly reduced expression of runx1, c-myb, mpo-1, Scl and pu.1, and significantly reduced o-dianisidine staining of haemoglobin. Systematically, miR-145 regulates haematopoiesis by repressing expression of meis1 involved in haematopoiesis. We performed knock-down analysis of the meis1 gene to check and demonstrate that whether meis1-EGFP is related with our miRNA. Co-injection-confirmation at 24 and 48 hpf pictures analyses showed that overexpression of miR-145 repressed expression of meis1. Bioinformatics analysis predicts a target binding sequence for miR-145 at the 3-UTR of meis1. Deletion of the miR-145 target sequence eliminated the repression of meis1 expression mediated by miR-145. These findings create miR-145 as a novel miRNA that regulates haematopoiesis and vascular development by repressing expression of meis1.