MicroRNA‑425 inhibits proliferation of chronic lymphocytic leukaemia cells through regulation of the Bruton's tyrosine kinase/phospholipase Cγ2 signalling pathway

  • Authors:
    • Jianying Chen
    • Yuhua Li
    • Xiaoling Xie
  • View Affiliations

  • Published online on: May 19, 2020     https://doi.org/10.3892/etm.2020.8771
  • Pages: 1169-1175
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Abstract

The present study aimed to investigate the effects of microRNA (miR)-425 on the proliferation of chronic lymphocytic leukaemia (CLL) cells and the possible underlying mechanisms. The expression of miR‑425 was determined in the B lymphocytes of CLL patients and in normal B lymphocytes by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In addition, MEC‑1 cells transfected with miR‑425 negative control (NC) or miR‑425 mimic were examined. The cell proliferation of different groups was evaluated using an MTT assay, and cell cycle distribution was evaluated using flow cytometry analysis. A dual‑luciferase reporter assay was used to verify whether Bruton's tyrosine kinase (BTK) was a target of miR‑425. Furthermore, the expression levels of BTK, phospholipase Cγ2 (PLCγ2), Ki‑67 and proliferating cell nuclear antigen (PCNA) were determined by RT‑qPCR and western blotting. The results revealed that the expression of miR‑425 was significantly downregulated in B lymphocytes obtained from CLL patients as compared with that in normal B lymphocytes. When cells were transfected with miR‑425 mimic, the proliferation of MEC‑1 cells was significantly inhibited at 24, 48 and 72 h compared with the proliferation of control cells. Additionally, the ratio of G0/G1 cells was significantly increased and the ratio of G2/M cells was significantly decreased in miR‑425‑overexpressing cells compared with that in control cells. The luciferase reporter assay revealed that miR‑425 binds to the 3'‑untranslated region of BTK mRNA. Finally, BTK, PLCγ2, Ki‑67 and PCNA expression was significantly inhibited at the mRNA and protein level in cells where miR‑425 was upregulated. In conclusion, miR‑425 inhibits the proliferation of MEC‑1 cells, potentially by inhibiting BTK/PLCγ2 signalling, and Ki‑67 and PCNA expression levels. These results provide a deeper insight for understanding the development of CLL and suggest a potential novel target for the treatment of CLL patients.

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August-2020
Volume 20 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Chen J, Li Y and Xie X: MicroRNA‑425 inhibits proliferation of chronic lymphocytic leukaemia cells through regulation of the Bruton's tyrosine kinase/phospholipase Cγ2 signalling pathway. Exp Ther Med 20: 1169-1175, 2020
APA
Chen, J., Li, Y., & Xie, X. (2020). MicroRNA‑425 inhibits proliferation of chronic lymphocytic leukaemia cells through regulation of the Bruton's tyrosine kinase/phospholipase Cγ2 signalling pathway. Experimental and Therapeutic Medicine, 20, 1169-1175. https://doi.org/10.3892/etm.2020.8771
MLA
Chen, J., Li, Y., Xie, X."MicroRNA‑425 inhibits proliferation of chronic lymphocytic leukaemia cells through regulation of the Bruton's tyrosine kinase/phospholipase Cγ2 signalling pathway". Experimental and Therapeutic Medicine 20.2 (2020): 1169-1175.
Chicago
Chen, J., Li, Y., Xie, X."MicroRNA‑425 inhibits proliferation of chronic lymphocytic leukaemia cells through regulation of the Bruton's tyrosine kinase/phospholipase Cγ2 signalling pathway". Experimental and Therapeutic Medicine 20, no. 2 (2020): 1169-1175. https://doi.org/10.3892/etm.2020.8771