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Differential roles of miR‐15a/16‐1 and miR‐497/195 clusters in immune cell development and homeostasis
- Source :
- The Febs Journal
- Publication Year :
- 2020
- Publisher :
- John Wiley and Sons Inc., 2020.
-
Abstract
- MicroRNAs (miRNAs) post‐transcriptionally repress almost all genes in mammals and thereby form an additional layer of gene regulation. As such, miRNAs impact on nearly every physiological process and have also been associated with cancer. Prominent examples of such miRNAs can be found in the miR‐15 family, composed of the bicistronic clusters miR‐15a/16‐1, miR‐15b/16‐2, and miR‐497/195. In particular, the miR‐15a/16‐1 cluster is deleted in almost two thirds of all chronic B lymphocytic leukemia (CLL) cases, a phenotype that is also recapitulated by miR‐15a/16‐1‐deficient as well as miR‐15b/16‐2‐deficient mice. Under physiological conditions, those two clusters have been implicated in T‐cell function, and B‐cell and natural killer (NK) cell development; however, it is unclear whether miR‐497 and miR‐195 confer similar roles in health and disease. Here, we have generated a conditional mouse model for tissue‐specific deletion of miR‐497 and miR‐195. While mice lacking miR‐15a/16‐1 in the hematopoietic compartment developed clear signs of CLL over time, aging mice deficient for miR‐497/195 did not show such a phenotype. Likewise, loss of miR‐15a/16‐1 impaired NK and early B‐cell development, whereas miR‐497/195 was dispensable for these processes. In fact, a detailed analysis of miR‐497/195‐deficient mice did not reveal any effect on steady‐state hematopoiesis or immune cell function. Unexpectedly, even whole‐body deletion of the cluster was well‐tolerated and had no obvious impact on embryonic development or healthy life span. Therefore, we postulate that the miR‐497/195 cluster is redundant to its paralog clusters or that its functional relevance is restricted to certain physiological and pathological conditions.<br />The miR‐15a/16‐1 and miR‐15b/16‐2 clusters regulate hematopoiesis and are key tumor suppressors in chronic lymphocytic leukemia. However, little is known about the third cluster of the miR‐15 family, miR‐497/195. Here, we show that miR‐497/195 is dispensable for immune cell development and function, and that its loss does not provoke any overt malignancies. This suggests a redundant role for miR‐497/195 or that its functional relevance is restricted to certain conditions.
- Subjects :
- 0301 basic medicine
Male
T-Lymphocytes
Biochemistry
Animals, Genetically Modified
Mice
0302 clinical medicine
Bone Marrow
miR‐195
Homeostasis
Sequence Deletion
Regulation of gene expression
Gene Editing
B-Lymphocytes
leukemia
Gene Expression Regulation, Developmental
Mouse Embryonic Stem Cells
Phenotype
Cell biology
Killer Cells, Natural
Leukemia
Haematopoiesis
030220 oncology & carcinogenesis
Original Article
Female
miR‐15
Single-Cell Analysis
Signal Transduction
Biology
Immunophenotyping
03 medical and health sciences
Immune system
miR‐497
microRNA
medicine
Animals
Humans
Molecular Biology
Gene
Cell Proliferation
Cell growth
Cell Biology
Original Articles
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
hematopoiesis
Disease Models, Animal
MicroRNAs
030104 developmental biology
Lymph Nodes
Spleen
Subjects
Details
- Language :
- English
- ISSN :
- 17424658 and 1742464X
- Volume :
- 288
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The Febs Journal
- Accession number :
- edsair.doi.dedup.....82310599e3a5e28ef169408d3b970d5b