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CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis

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 ass...

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Autores principales: Luo, Cong, Li, Jun-Jun, Wen, Feng, Cao, Yi-Xiong, Luo, Ze-Yu, Long, Xing-Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091256/
https://www.ncbi.nlm.nih.gov/pubmed/35538053
http://dx.doi.org/10.1038/s41420-022-00857-1
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author Luo, Cong
Li, Jun-Jun
Wen, Feng
Cao, Yi-Xiong
Luo, Ze-Yu
Long, Xing-Xing
author_facet Luo, Cong
Li, Jun-Jun
Wen, Feng
Cao, Yi-Xiong
Luo, Ze-Yu
Long, Xing-Xing
author_sort Luo, Cong
collection PubMed
description 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.
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spelling pubmed-90912562022-05-12 CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis Luo, Cong Li, Jun-Jun Wen, Feng Cao, Yi-Xiong Luo, Ze-Yu Long, Xing-Xing Cell Death Discov Article 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. Nature Publishing Group UK 2022-05-10 /pmc/articles/PMC9091256/ /pubmed/35538053 http://dx.doi.org/10.1038/s41420-022-00857-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Luo, Cong
Li, Jun-Jun
Wen, Feng
Cao, Yi-Xiong
Luo, Ze-Yu
Long, Xing-Xing
CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis
title CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis
title_full CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis
title_fullStr CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis
title_full_unstemmed CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis
title_short CircFBXW7 inhibits the tumorigenesis of T-cell acute lymphoblastic leukemia through modulating miR-494-3p/SOX1 axis
title_sort circfbxw7 inhibits the tumorigenesis of t-cell acute lymphoblastic leukemia through modulating mir-494-3p/sox1 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091256/
https://www.ncbi.nlm.nih.gov/pubmed/35538053
http://dx.doi.org/10.1038/s41420-022-00857-1
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