Blood:miR-29 regulates the CD40 signal in the CLL micro environment via TRAF4

B-cell-induced (BCR) signal transductivity and T-cell interaction play a key role in the pathogenesis and course progression of chronic lymphocytic leukemia (CLL).
cells can use microRNAs (MiRNAs) and their target genes to regulate micro-environmental interactions in lymph node niches.
To determine the expression changes of miRNA in the CLL micro-environment, the researchers performed a complex map analysis of short-chain non-coding RNA by comparing CXCR4/CD5 cloned inner cell sub-groups (CXCR4dimCD5bright and CXCR4bright CD5dim cells).
miRNAs for differential expression of two sub-group cells were found, several of which have been shown to be involved in regulating BCR signals miRNAs (miR-155, miR-150, and miR-22).
it is worth noting that all members of the miR-29 family (miR-29a, miR-29b, miR-29c) continued to decrease in the immunologic micro-environment, and that the decrease in miR-29 (a/b/c) levels was associated with increased relative responsiveness of CLL cells to BCR blocking and a significant reduction in the overall survival of CLL patients.
the relationship between the expression level of
miR-29 and total lifetime, the researchers also found that tumor necrotogenic factor 4 (TRAF4) is a new direct target for miR-29s, and that high TRAF4 levels can increase the CRL's response to CD40 activation and downstream NFkB signals.
in the CLL, BCR suppresses the expression of miR-29 through MYC, while allowing TRAF4 to go up and CD40-NFkB signal enhancement.
the regulatory loop can be destroyed by "BCR inhibitors" (BTK inhibitors erudinib or PI3K inhibitors idelalisib).
summary model diagram, the study demonstrates for the first time the miRNA-dependent mechanism for activating CD40 signal/T cell interactions in the CLL micro-environment, and describes a new miR-29-TRAF4-CD40 signal axis regulated by BCR activity.
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