PT  - JOURNAL ARTICLE
AU  - Hutter, Katharina
AU  - Lindner, Silke E
AU  - Kurschat, Constanze
AU  - Rülicke, Thomas
AU  - Villunger, Andreas
AU  - Herzog, Sebastian
TI  - The miR-26 family regulates early B cell development and transformation
AID  - 10.26508/lsa.202101303
DP  - 2022 Aug 01
TA  - Life Science Alliance
PG  - e202101303
VI  - 5
IP  - 8
4099  - https://www.life-science-alliance.org/content/5/8/e202101303.short
4100  - https://www.life-science-alliance.org/content/5/8/e202101303.full
SO  - Life Sci. Alliance2022 Aug 01; 5
AB  - MiRNAs are small noncoding RNAs that promote the sequence-specific repression of their respective target genes, thereby regulating diverse physiological as well as pathological processes. Here, we identify a novel role of the miR-26 family in early B cell development. We show that enhanced expression of miR-26 family members potently blocks the pre-B to immature B cell transition, promotes pre-B cell expansion and eventually enables growth factor independency. Mechanistically, this is at least partially mediated by direct repression of the tumor-suppressor Pten, which consequently enhances PI3K-AKT signaling. Conversely, limiting miR-26 activity in a more physiological loss-of-function approach counteracts proliferation and enhances pre-B cell differentiation in vitro as well as in vivo. We therefore postulate a rheostat-like role for the miR-26 family in progenitor B cells, with an increase in mature miR-26 levels signaling cell expansion, and facilitating pre-B to the immature B cell progression when reduced.