Luo Cong, Li Jun-Jun, Wen Feng, Cao Yi-Xiong, Luo Ze-Yu, Long Xing-Xing
Department of Hematology, the First Affiliated Hospital, Hengyang Medical school, University of South China, Hengyang421001, Hengyang, Hunan Province, China.
Cell Death Discov. 2022 May 10;8(1):256. doi: 10.1038/s41420-022-00857-1.
T-cell acute lymphoblastic leukemia (T-ALL) is a type of leukemia with high malignant behaviors, which seriously threatens the health of people. It has been reported that circFBXW7 is downregulated in lymphoblastic leukemia. Nevertheless, the exact role of circFBXW7 in T-ALL remains elusive. MTT assay was used to assess the cell viability. Cell apoptosis was assessed by flow cytometry. In addition, mRNA expressions were assessed by RT-qPCR, and a western blot was applied to investigate the protein levels. Meanwhile, the correlation among circFBXW7, miR-494-3p, and SOX1 was explored by RNA pull-down and dual-luciferase reporter assays. Furthermore, a xenograft mice model was conducted to verify the function of circFBXW7 in T-ALL in vivo. CircFBXW7 was significantly downregulated in T-ALL, of which overexpression inhibited the cell viability and induced the apoptosis of Jurkat cells. Moreover, miR-494-3p was identified to be a functional downstream effector to be involved in circFBXW7-mediated T-ALL cell proliferation. Besides, SOX1 was a direct target of miR-494-3p, and the impact of miR-494-3p mimics on T-ALL cell growth was inhibited in the presence of SOX1 overexpression. Furthermore, overexpression of circFBXW7 dramatically inhibited T-ALL tumor growth. In summary, circFBXW7 attenuated the tumorigenesis of T-ALL through the mediation of the miR-494-3p/SOX1 axis, which might be novel targets for T-ALL treatment.
T细胞急性淋巴细胞白血病（T-ALL）是一种具有高度恶性行为的白血病，严重威胁人类健康。据报道，环状FBXW7在淋巴细胞白血病中表达下调。然而，环状FBXW7在T-ALL中的确切作用仍不清楚。采用MTT法评估细胞活力。通过流式细胞术评估细胞凋亡。此外，通过RT-qPCR评估mRNA表达，并应用蛋白质免疫印迹法研究蛋白质水平。同时，通过RNA下拉实验和双荧光素酶报告基因实验探究环状FBXW7、miR-494-3p和SOX1之间的相关性。此外，构建异种移植小鼠模型以在体内验证环状FBXW7在T-ALL中的功能。环状FBXW7在T-ALL中显著下调，其过表达抑制Jurkat细胞的活力并诱导其凋亡。此外，miR-494-3p被确定为参与环状FBXW7介导的T-ALL细胞增殖的功能性下游效应分子。此外，SOX1是miR-494-3p的直接靶标，在SOX1过表达的情况下，miR-494-3p模拟物对T-ALL细胞生长的影响受到抑制。此外，环状FBXW7的过表达显著抑制T-ALL肿瘤生长。综上所述，环状FBXW7通过miR-494-3p/SOX1轴的介导减弱了T-ALL的肿瘤发生，这可能是T-ALL治疗的新靶点。
