Knockdown of TRIM24 suppresses growth and induces apoptosis in acute myeloid leukemia through downregulation of Wnt/GSK-3β/β-catenin signaling

Abstract

Tripartite motif-containing protein 24 (TRIM24) has currently emerged as a crucial cancer-related gene present in a wide range of human cancer types. However, the involvement of TRIM24 in acute myeloid leukemia (AML) has not been well investigated. The present study aims to investigate the significance, cellular function, and potential regulatory mechanism of TRIM24 in AML. We found that TRIM24 expression was significantly upregulated in AML compared with normal tissues. AML patients with low expression of TRIM24 had higher survival rates than those expressing TRIM24 at higher levels. High expression of TRIM24 was also detected in AML cells and its knockdown markedly restricted proliferation and promoted apoptosis in AML cells. Further investigation revealed that TRIM24 contributed to the regulation of Wnt/β-catenin signaling, which was associated with modulating the phosphorylation status of glycogen synthase kinase-3β (GSK-3β). Inactivation of GSK-3β partially reversed the TRIM24 knockdown-mediated antitumor effects observed in AML cells. Furthermore, knockdown of TRIM24 retarded the growth of AML-derived xenograft tumors in nude mice in vivo. Overall, these findings demonstrate that knockdown of TRIM24 impedes the AML tumor growth through the modulation of Wnt/GSK-3β/β-catenin signaling. These findings highlight the potential TRIM24 as an attractive anticancer target to treat AML.

Long noncoding RNA SATB1-AS1 contributes to the chemotherapy resistance through the microRNA-580/ 2’-5’-oligoadenylate synthetase 2 axis in acute myeloid leukemia

“…More specifically, the GSK-3β inhibitor AR-A014418 held the capacity of eliminating the repressive role of si-SATB1-AS1 on AML cell resistance in the current report. Consistent findings were reported before where inactivation of GSK3β partially reversed the TRIM24 knockdownmediated antitumor effects in AML cells [38].…”

Identification of proximal SUMO-dependent interactors using SUMO-ID

“…While many of the SUMO-ID candidates show increased peptide intensity in PML NBs after ATO treatment, we observed that some of them decreased. IRF2BP2 and TRIM24, which has also been linked to AML 56,57 , showed reduced levels after ATO treatment, suggesting that they might undergo degradation. In line with this idea, the 11S proteasome components are recruited into mature PML NBs and their localization is enhanced with ATO treatment 58 , suggesting that mature PML NBs may also act as proteolytic sites.…”

The significance of CUX1 and chromosome 7 in myeloid malignancies

“…Germline À/À mice develop hepatocellular carcinoma but have no hematopoietic phenotype [46] No High expression in AML reported, associated with poor survival [45] Targets p53 for degradation [44] Decreased proliferation in AML- Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. [98].…”