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

• Published in: Human & experimental toxicology 2020-12, Vol.39 (12), p.1725-1736
• Main Authors: Li, C, Xin, H, Shi, Y, Mu, J
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Animals; Anticancer properties; Antitumor activity; Apoptosis; beta Catenin - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line, Tumor; Cell proliferation; Deactivation; Down-Regulation; Gene Knockdown Techniques; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - metabolism; Glycogens; Humans; Inactivation; Investigations; Kaplan-Meier Estimate; Kinases; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - mortality; Mice, Inbred BALB C; Mice, Nude; Myeloid leukemia; Phosphorylation; Prognosis; Regulatory mechanisms (biology); Signaling; Survival; Tumors; Wnt protein; Wnt Signaling Pathway; Xenografts; Xenotransplantation; β-Catenin
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327120938845

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.