Publication Date
3-8-2022
Journal
Cell Reports
DOI
10.1016/j.celrep.2022.110481
PMID
35263585
PMCID
PMC11185845
PubMedCentral® Posted Date
6-18-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Cell Line, Tumor, Cell Self Renewal, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, MicroRNAs, Receptors, Cytoplasmic and Nuclear, Repressor Proteins
Abstract
Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA and protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this critical nexus. Here, we identify miR-130a as a regulator of HSC self-renewal and differentiation. Enforced expression of miR-130a impairs B lymphoid differentiation and expands long-term HSCs. Integration of protein mass spectrometry and chimeric AGO2 crosslinking and immunoprecipitation (CLIP) identifies TBL1XR1 as a primary miR-130a target, whose loss of function phenocopies miR-130a overexpression. Moreover, we report that miR-130a is highly expressed in t(8;21) acute myeloid leukemia (AML), where it is critical for maintaining the oncogenic molecular program mediated by the AML1-ETO complex. Our study establishes that identification of the comprehensive miRNA targetome within primary cells enables discovery of genes and molecular networks underpinning stemness properties of normal and leukemic cells.
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Biochemical Phenomena, Metabolism, and Nutrition Commons, Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Genetic Phenomena Commons, Genetic Processes Commons, Medical Genetics Commons, Medical Specialties Commons
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