hsa-miR-106b

chronic lymphocytic leukemia (CLL)

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

Itch

Validated targets of miRNA from TarBase:

unknown : More...

Description:

Chronic lymphocytic leukemia (CLL) is characterized by cells that exhibit dysfunctional apoptosis. Here, we show, deacetylase inhibition led to the E2F1- and myc-mediated transcriptional activation of the microRNA, miR106b in primary CLL cells. Induction of miR106b was associated with a downregulation in the levels of the E3-ubiquitin ligase, Itch. Decreases in Itch protein levels were associated with a reciprocal accumulation of its proapoptotic substrate, TAp73 (p73), and induction of PUMA mRNA and protein. Ectopic expression of miR106b in CLL cells demonstrated that Itch was a direct target of miR106b such that miR106b-induced decreases in Itch resulted in an accumulation of p73. Thus, our results identify a novel regulatory mechanism wherein miRNA regulate cell survival by mediating the post-transcriptional downregulation of an ubiquitin ligase, leading to the induction of a proapoptotic regulator in malignant cells. Silencing of miRNA expression in CLL may selectively suppress proapoptotic pathways providing such tumors with a survival advantage. Consequently, chemotherapeutic drugs that activate miR106b could initiate a p53-independent mechanism that targets CLL cells.

Reference:

Specific activation of microRNA106b enables the p73 apoptotic response in chronic lymphocytic leukemia by targeting the ubiquitin ligase, Itch for degradation. | PMID:19096009
Sampath D, Calin GA, Puduvalli VK, Gopisetty G, Taccioli C, Liu CG, Ewald B, Liu C, Keating MJ, Plunkett W.
Blood. 2008 Dec 18. [Epub ahead of print]