Over-expression of miR-196b-5p is significantly associated with the progression of myelodysplastic syndrome

Abstract

Myelodysplastic syndrome (MDS) is a clonal stem cell disorder characterized by ineffective hematopoiesis with a high risk of transformation to acute myeloid leukemia (AML). miRNAs function as tumor suppressors and oncogenes in various cancers and regulate the differentiation potential of hematopoietic stem and progenitor cells (HSPCs). It has been suggested that miRNAs may play an important role in progression of MDS. We analyzed bone marrow samples collected from MDS patients according to different risk stratification indicated by the International Prognostic Scoring System (IPSS). We demonstrated that miR-196b-5p was up-regulated in intermediate II and higher groups, and in secondary AML (s-AML) patients in particular (P < 0.01) compared with healthy controls, suggesting that the higher expression levels are associated with increased risk of the development of MDS. We observed changes in proliferation and apoptosis in MDS-L cells following transfection with miR-196-5p mimics or inhibitors. After up-regulating the expression of miR-196b-5p, proliferation of MDS-L cells was up-regulated, whereas apoptosis was down-regulated (P < 0.05). In contrast, down-regulation of miR-196b-5p expression decreased cell proliferation and increased apoptosis (P < 0.05). We concluded that over-expression of miR-196b-5p may be closely associated with the risk of transformation to leukemia in MDS patients.

Analysis of long non-coding RNAs in neonatal piglets at different stages of porcine deltacoronavirus infection

“…miR-490-5p inhibits cell proliferation, migration and invasion but miR-490-5p can promote apoptosis of Human hepatoma (Hep3B) cells by inhibiting Roundabout Guidance Receptor 1 (ROBO1) [31]. MiR-196b-5p overexpression may also be associated with a risk of conversion of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) [32]. The target miRNAs ssc-miR-194b-3p, ssc-miR-184, ssc-miR-215, ssc-miR-874 were all down regulated.…”

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

“…MiRNAs simultaneously targeting intracellular pathways are involved in a broad range of (patho)physiologic processes. They are critical regulators of hematopoiesis and their aberrant expression has been associated with various types of leukemia [ 35 , 36 , 39 ] Their functional role in the context of MDS and sAML is under debate due to methodical differences and the source/material profiled for miRNA expression in both diseases [ 38 , 39 , 94 , 96 , 100 , 123 , 124 , 125 , 126 ]. Sorted CD34 + BM cells still comprise a heterogeneous cell population and not all neoplastic blasts in MDS and sAML express CD34 [ 85 ].…”

“…Again, these studies significantly differed with regard to the cellular source investigated. While some studies used unsorted BM cells [ 100 , 123 ] others examined mononuclear cells [ 38 , 39 ] [ 94 , 96 , 124 , 125 ] or CD34 + BM cells [ 126 ], respectively. It is noteworthy that each investigative approach has its own advantages and disadvantages.…”

Prognostic Markers of Myelodysplastic Syndromes

“…Analysis of literature data showed that miRNA expression profiles differ between early and advanced stages of MDS, suggesting the involvement of miRNAs in the pathogenesis of MDS and, consequently, in MDS-to-AML transformation [ 99 ]. The expression levels of miRNA-27a-3p, −150-5p, −199a-5p, −223-3p and miRNA-451a are reduced in the plasma of high-risk patients with MDS, while miRNA-196b-5p is enhanced in BM specimens from a higher-risk patient with MDS, suggesting that these miRNAs may be used as biomarkers predicting the risk of further transformation of MDS [ 100 , 101 ]. Elevated miRNA-661 and miRNA-125a are negatively correlated with survival in MDS [ 102 , 103 ].…”