Suppression of miR-708 inhibits the Wnt/ β-catenin signaling pathway by activating DKK3 in adult B-all.

Suppression of miR-708 inhibits the Wnt/β-catenin signaling pathway by activating DKK3 in adult B-all. Oncotarget. 2017 Jul 18;: Authors: Zhang Y, Li H, Cao R, Sun L, Wang Y, Fan S, Zhao Y, Kong D, Cui L, Lin L, Wang K, Li Y, Zhou J Abstract Inactivation of Dickkopf-3 (DKK3) is closely associated with a poor prognosis in various solid tumor and hematologic malignancies. Promoter hypermethylation is one potential cause of DKK3 inactivation. However, whether other mechanisms lead to DKK3 inactivation and the subsequent effects of these inactivations on cell proliferation and the Wnt signaling pathway in adult B acute lymphoblastic leukemia (B-ALL) remain unclear. In the present study, we found that low DKK3 expression levels were associated with high miR-708 expression and promoter hypermethylation in adult B-ALL. miR-708 was confirmed to directly decrease DKK3 expression in Nalm-6 and BALL-1 cells. Additionally, a miR-708 inhibitor decreased cell proliferation mainly through apoptosis and cell cycle arrest at the G1 phase, and these effects were eliminated by DKK3 siRNA treatment. Moreover, the demethylating agent 5-aza-2'-deoxycytidine (5-aza) decreased the methylation state of the DKK3 promoter based on methylation-specific PCR (MSP) and bisulfite genomic sequencing PCR (BSP), although this demethylation effect was not enhanced by the miR-708 inhibitor. The miR-708 inhibitor or 5-aza significantly increased DKK3 expression and decr...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research