mir-223

In molecular biology MicroRNA-223 (miR-223) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-223 is a hematopoietic specific microRNA with crucial functions in myeloid lineage development. It plays an essential role in promoting granulocytic differentiation while also being associated with the suppression of erythrocytic differentiation. miR-223 is commonly repressed in hepatocellular carcinoma and leukemia. Higher expression levels of miRNA-223 are associated with extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach and recurrent ovarian cancer. In some cancers the microRNA-223 down-regulation is correlated with higher tumor burden, disease aggressiveness, and poor prognostic factors. MicroRNA-223 is also associated with rheumatoid arthritis, sepsis, type 2 diabetes, and hepatic ischemia. In molecular biology MicroRNA-223 (miR-223) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-223 is a hematopoietic specific microRNA with crucial functions in myeloid lineage development. It plays an essential role in promoting granulocytic differentiation while also being associated with the suppression of erythrocytic differentiation. miR-223 is commonly repressed in hepatocellular carcinoma and leukemia. Higher expression levels of miRNA-223 are associated with extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach and recurrent ovarian cancer. In some cancers the microRNA-223 down-regulation is correlated with higher tumor burden, disease aggressiveness, and poor prognostic factors. MicroRNA-223 is also associated with rheumatoid arthritis, sepsis, type 2 diabetes, and hepatic ischemia. MicroRNA-223 was initially identified bioinformatically and it was subsequently characterized as part of the haematopoietic system. Its gene resembles a myeloid gene and it could be driven by the PU.1 and C/EBPα proteins which are myeloid transcription factors. MicroRNA-223 selectively targets distinct populations of transcripts harboring AU-rich elements. More specifically, it was validated that the RhoB mRNA is a bona fide miR-223 target. miR-223 also regulates cyclin E activity by modulating expression of the FBXW7 protein. In particular, overexpression of miR-223 reduces FBXW7 mRNA levels while increasing endogenous cyclin E protein and activity levels. The role of miR-223 in hematopoiesis has been extensively analyzed in the past few years. During granulopoiesis miR-223 acts as fine-tuner of granulocytic differentiation, maturation, and function. More specifically, human granulocytic differentiation is controlled by a regulatory circuitry involving miR-223 and two transcriptional factors, NFIA and C/EBPα. These two factors compete for binding: NFI-A maintains miR-223 at low levels whereas C/EBPα upregulates miR-223 expression. The competition by C/EBPα and the granulocytic differentiation are favored by a negative-feedback loop in which miR-223 represses NFI-A translation. Analysis of expression profiles indicate that miR-223 expression decreases as cells mature during monocytic, erythroid, and mast cell differentiation. miR-223 down-regulation during erythropoiesis is required for erythrocyte proliferation and differentiation at progenitor and precursor level. This down-modulation promotes erythropoiesis favoring translation of the key functional protein LMO2 resulting in reversible regulation of erythroid and megakaryocytic differentiation. MicroRNA-223 also plays an essential role during osteoclast differentiation. More specifically, miR-223 expression suppresses the differentiation of osteoclast precursors into osteoclast thus making it a potential viable therapeutic target for a range of bone metabolic disorders with excess osteoclast activity. MicroRNA-223 is commonly repressed in hepatocellular carcinoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, gastric MALT lymphoma, and recurrent ovarian cancer. Integrative analysis in hepatocellular carcinoma implicates Stathmin 1 (STMN1) as a downstream target of miR-223. Furthermore, miR-223 could suppress the luciferase activity in reporter construct containing the STMN1 3' untranslated region. The reduced expressions of miR-223 may predispose to the development of hepatocellular carcinoma via the widespread induction of chromosomal instability by STMN1. MicroRNA-223 blocks the translation of E2F1 leading to inhibition of cell-cycle progression followed by myeloid differentiation. In acute myeloid leukemia (AML), miR-223 is down-regulated thus leading to E2F1 overexpression. The overexpressed E2F1 could bind to the miR-223 promoter and in turn lead to a further decrease in miR-223 expression through a negative feedback loop followed by myeloid cell-cycle progression at the expense of differentiation. Overexpression of E2F1 has been shown to be an oncogenic event that predisposes cells to transformation. While there is some indication of the miR-223 role in AML there is still little known about this microRNA function in chronic lymphocytic and acute lymphoblastic leukemia. Nevertheless, MicroRNA-223 expression levels decreased significantly with the progression of these two diseases thus associating miR-223 down-regulation with higher tumor burden, disease aggressiveness, and poor prognostic factors.