期刊
MOLECULAR BIOTECHNOLOGY
卷 64, 期 12, 页码 1419-1430出版社
SPRINGERNATURE
DOI: 10.1007/s12033-022-00476-2
关键词
HES1; Notch1; PTEN; Chronic lymphocytic leukemia; Proliferation; Apoptosis
资金
- General items of Health Department of Zhejiang Province [2021KY1078]
- Zhejiang Provincial Health Science and Technology Plan in 2022 (Clinical Research Application Project) [2022KY350]
- Wenzhou Science and Technology Bureau [Y20210155]
This study reveals that the high expression of HES1 and Notch1, as well as the low expression of PTEN, is associated with poor prognosis in CLL patients. Activation of the HES1-mediated Notch1 signaling pathway promotes CLL cell proliferation and inhibits apoptosis.
Hairy and enhancer of split homolog-1 (HES1), regulated by the Notch, has been reported to play important roles in the immune response and cancers, such as leukemia. In this study, we aim to explore the effect of HES1-mediated Notch1 signaling pathway in chronic lymphocytic leukemia (CLL). Reverse transcription quantitative polymerase chain reaction and Western blot assay were conducted to determine the expression of HES1, Notch1, and PTEN in B lymphocytes of peripheral blood samples of 60 CLL patients. We used lentivirus-mediated overexpression or silencing of HES1 and the Notch1 signaling pathway inhibitor, MW167, to detect the interaction among HES1, Notch1, and PTEN in CLL MEC1 and HG3 cells. MTT assay and flow cytometry were employed for detection of biological behaviors of CLL cells. HES1 and Notch1 showed high expression, but PTEN displayed low expression in B lymphocytes of peripheral blood samples of patients with CLL in association with poor prognosis. HES1 bound to the promoter region of PTEN and reduced PTEN expression. Overexpression of HES1 activated the Notch1 signaling pathway, thus promoting the proliferation of CLL cells, increasing the proportion of cells arrested at the S phase and limiting the apoptosis of CLL cells. Collectively, HES1 can promote activation of the Notch1 signaling pathway to cause PTEN transcription inhibition and the subsequent expression reduction, thereby promoting the proliferation and inhibiting the apoptosis of CLL cells.
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