Qu Honglan, Gao-Wa Hasen, Hou Yanyan, Ren Mengwei, Li Jun, Jing Baoshong, Du YanDan
Department of Hematology and Oncology, Inner Mongolia Forestry General Hospital, The Second Clinical Medical College of Inner Mongolia University for Nationalities, Yakeshi, China.
Front Oncol. 2023 Feb 27;12:1016725. doi: 10.3389/fonc.2022.1016725. eCollection 2022.
TRIM37 has been reported to be associated with the tumorigenesis of cancers. However, the role of TRIM37 in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. This study aimed to characterize the effect of TRIM37 on T-ALL.
TRIM37 expression in T-ALL patients and T-ALL cell lines was determined by qRT-PCR and Western blot. Knockdown or overexpression of TRIM37 was conducted by transferring small-interfering TRIM37 or lentivirus-mediated transducing into T-ALL cells. CCK-8 assay and flow cytometry assay were conducted to analyze the proliferation and apoptosis of T-ALL cells. Co-immunoprecipitation experiments were conducted to investigate the relationship between TRIM37 and PTEN and the ubiquitination of PTEN.
Our results suggested that TRIM37 expression was upregulated in the blood of T-ALL patients and T-ALL cell lines. Knockdown of TRIM37 noticeably inhibited the proliferation and promoted apoptosis of T-ALL cells. Ectopic expression of TRIM37 promoted the proliferation and suppressed the apoptosis rate of MOLT-4 cells and enhanced the phosphorylation of AKT. Moreover, TRIM37 interacted with PTEN and accelerated the degradation of PTEN TRIM37-mediated ubiquitination in T-ALL cells. Moreover, TRIM37 reduced the sensitivity of T-ALL cells to bortezomib treatment. Additionally, PI3K/AKT signaling pathway was involved in the function of TRIM37 in T-ALL. TRIM37 contributed to the proliferation of T-ALL cells and reduced the susceptibility of T-ALL cells to bortezomib treatment through ubiquitination of PTEN and activating PI3K/AKT signaling pathway.
Our study suggested that TRIM37 could be considered as a therapeutic target for T-ALL.
据报道，TRIM37与癌症的肿瘤发生有关。然而，TRIM37在T细胞急性淋巴细胞白血病（T-ALL）中的作用仍不清楚。本研究旨在阐明TRIM37对T-ALL的影响。
通过qRT-PCR和蛋白质免疫印迹法检测T-ALL患者血液及T-ALL细胞系中TRIM37的表达。通过转染小干扰TRIM37或慢病毒介导的转导至T-ALL细胞中来实现TRIM37的敲低或过表达。采用CCK-8法和流式细胞术分析T-ALL细胞的增殖和凋亡情况。进行免疫共沉淀实验以研究TRIM37与PTEN之间的关系以及PTEN的泛素化情况。
我们的结果表明，TRIM37在T-ALL患者血液及T-ALL细胞系中表达上调。敲低TRIM37可显著抑制T-ALL细胞的增殖并促进其凋亡。TRIM37的异位表达促进了MOLT-4细胞的增殖，抑制了其凋亡率，并增强了AKT的磷酸化。此外，TRIM37与PTEN相互作用并加速了PTEN的降解，这是TRIM37在T-ALL细胞中介导的泛素化作用。此外，TRIM37降低了T-ALL细胞对硼替佐米治疗的敏感性。另外，PI3K/AKT信号通路参与了TRIM37在T-ALL中的功能。TRIM37通过PTEN的泛素化和激活PI3K/AKT信号通路，促进了T-ALL细胞的增殖并降低了T-ALL细胞对硼替佐米治疗的敏感性。
我们的研究表明，TRIM37可被视为T-ALL的治疗靶点。
