Journal of Practical Oncology ›› 2022, Vol. 36 ›› Issue (5): 404-410.doi: 10.11904/j.issn.1002-3070.2022.05.003

• Basic Research • Previous Articles     Next Articles

lncRNA XIST regulates the proliferation and invasion of acute T lymphocytic leukemia through the miR-375-Notch1 axis

LU Xiaoqin1, LEI Jiaojiao1, LIU Yuxin1, ZHAO Huaqing2   

  1. 1. Department of Pharmacy and Laboratory Medicine,Ya'an Vocational College,Yaan 625000,China;
    2. Department of Emergency,Three Gorges Hospital Affiliated to Chongqing University
  • Received:2021-09-24 Revised:2022-05-30 Online:2022-10-28 Published:2022-11-10

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Abstract: Objective The aim of this study was to investigate the effect of lncRNA XIST on the proliferation and invasion of T-acute lymphocytic leukemia(T-ALL)cells through the regulation of miR-375-Notch1 axis. Methods Fifty-seven patients with T-ALL who were treated from June 2018 to March 2021 were collected as the observation object(T-ALL group),and 55 healthy people who underwent physical examination during the same period were selected as the control group.The levels of lncRNA XIST in the two groups of patients and CCRF-CEM cell lines were detected by qRT-PCR;CCRF-CEM cells were transfected with si-lncRNA XIST to silence lncRNA XIST,and miR-375 mimics were transfected to overexpress miR-375.CCK-8 method,transwell invasion test and flow cytometry were used to detect the proliferation,invasion and apoptosis of CCRF-CEM cells;the luciferase reporter gene method was used to detect lncRNA XIST target gene;Western blot was used to detect the expressions of Notch1,ADAM-17 and Hes1 protein. Results Compared with the control group,the expression of lncRNA XIST and Notch1 mRNA in the T-ALL group was significantly increased(P＜0.05),while the level of miR-375 was significantly decreased(P＜0.05),and the level of Notch1 protein in T-ALL patients was significantly higher than that in the control group(P＜0.001).After transfection with si-lncRNA XIST to silence lncRNA XIST,the proliferation and invasion of CCRF-CEM cells were significantly decreased(P＜0.05),and the apoptosis was significantly increased(P＜0.05).The luciferase reporter gene revealed that miR-375 was the target of lncRNA XIST.After CCRF-CEM cells were transfected with miR-375,the number of cell proliferation and invasion were significantly decreased(P＜0.05),and the apoptosis was significantly increased(P＜0.05).Transfection of si-lncRNA XIST could significantly up-regulate the level of miR-375,down-regulate the level of Notch1 mRNA,and down regulate the expression of Notch1,ADAM-17 and Hes1 protein(P＜0.05). Conclusion lncRNA XIST is highly expressed in T-ALL patients,which may affect the biological function of leukemia cells through the miR-375-Notch1 axis.

Key words: T-acute lymphocytic leukemia, lncRNA XIST, miR-375, Notch1

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