PUBLICATION
MIR144 and MIR451 regulate human erythropoiesis via RAB14
- Authors
- Kim, M., Tan, Y.S., Cheng, W.C., Kingsbury, T.J., Heimfeld, S., Civin, C.I.
- ID
- ZDB-PUB-141015-3
- Date
- 2015
- Source
- British journal of haematology 168(4): 583-97 (Journal)
- Registered Authors
- Kim, Min Jung
- Keywords
- MIR144, MIR451, RAB14, erythropoietic inhibitor, human erythropoiesis
- MeSH Terms
-
- Cell Line, Tumor
- Erythroid Precursor Cells/cytology
- Erythroid Precursor Cells/drug effects
- Erythropoiesis/physiology*
- Erythropoietin/pharmacology
- Gene Expression Regulation
- Genetic Vectors/genetics
- Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
- Humans
- Lentivirus/genetics
- Leukemia, Erythroblastic, Acute/pathology
- MicroRNAs/antagonists & inhibitors
- MicroRNAs/biosynthesis
- MicroRNAs/genetics
- MicroRNAs/physiology*
- RNA Interference
- RNA, Small Interfering/pharmacology
- Recombinant Proteins/pharmacology
- Repressor Proteins/biosynthesis
- Repressor Proteins/genetics
- Transduction, Genetic
- Tumor Suppressor Proteins/biosynthesis
- Tumor Suppressor Proteins/genetics
- rab GTP-Binding Proteins/antagonists & inhibitors
- rab GTP-Binding Proteins/biosynthesis
- rab GTP-Binding Proteins/genetics
- rab GTP-Binding Proteins/physiology*
- PubMed
- 25312678 Full text @ Br. J. Haematol.
Citation
Kim, M., Tan, Y.S., Cheng, W.C., Kingsbury, T.J., Heimfeld, S., Civin, C.I. (2015) MIR144 and MIR451 regulate human erythropoiesis via RAB14. British journal of haematology. 168(4):583-97.
Abstract
Expression levels of MIR144 and MIR451 increase during erythropoiesis, a pattern that is conserved from zebrafish to humans. As these two miRs are expressed from the same polycistronic transcript, we manipulated MIR144 and MIR451 in human erythroid cells individually and together to investigate their effects on human erythropoiesis. Inhibition of endogenous human MIR451 resulted in decreased numbers of erythroid (CD71(hi) CD235a(hi) CD34(-) ) cells, consistent with prior studies in zebrafish and mice. In addition, inhibition of MIR144 impaired human erythroid differentiation, unlike in zebrafish and mouse studies where the functional effect of MIR144 on erythropoiesis was minimal. In this study, we found RAB14 is a direct target of both MIR144 and MIR451. As MIR144 and MIR451 expression increased during human erythropoiesis, RAB14 protein expression decreased. Enforced RAB14 expression phenocopied the effect of MIR144 and/or MIR451 depletion, whereas shRNA-mediated RAB14 knockdown protected cells from MIR144 and/or MIR451 depletion-mediated erythropoietic inhibition. RAB14 knockdown increased the frequency and number of erythroid cells, increased β-haemoglobin expression, and decreased CBFA2T3 expression during human erythropoiesis. In summary, we utilized MIR144 and MIR451 to identify RAB14 as a novel physiological inhibitor of human erythropoiesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping