Downregulation of Polo-like kinase 4 induces cell apoptosis and G2/M arrest in acute myeloid leukemia

作者全名："Chen, Shuyu; Zhong, Liang; Chu, Xuan; Wan, Peng; Liu, Zhenyan; Lu, Yang; Zhang, Zhonghui; Wang, Xiao; Zhou, Ziwei; Shao, Xin; Liu, Beizhong"

作者地址："[Chen, Shuyu; Chu, Xuan; Wan, Peng; Liu, Zhenyan; Lu, Yang; Zhang, Zhonghui; Wang, Xiao; Zhou, Ziwei; Shao, Xin; Liu, Beizhong] Chongqing Med Univ, Yongchuan Hosp, Cent Lab, Chongqing 402160, Peoples R China; [Zhong, Liang; Liu, Beizhong] Chongqing Med Univ, Dept Lab Med, Key Lab Lab Med Diagnost, Minist Educ, Chongqing 400016, Peoples R China"

通信作者："Liu, BZ (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Cent Lab, Chongqing 402160, Peoples R China."

来源：PATHOLOGY RESEARCH AND PRACTICE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000989921100001

JCR分区：Q2

影响因子：2.9

年份：2023

卷号：243

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Polo-like kinase 4; Acute myeloid leukemia; Centrinone; Endoplasmic reticulum stress; Cell Cycle; Cell apoptosis

摘要："Background: Polo-like kinase 4 (PLK4) is a crucial regulator for centriole replication and is reported to be aberrantly expressed in various cancers, where it participates to tumorigenesis. However, PLK4 effect in acute myeloid leukemia (AML), is still uncertain. This study investigates the function of PLK4 in AML.Methods: Quantitative real-time PCR was used to measure the level of PLK4. Centrinone, a selective PLK4 small molecule inhibitor, was used for PLK4 inhibition and explore its effect in AML cells. The cell growth was detected by the CCK8, while the cell cycle and apoptosis were assessed by flow cytometry. The level of proteins associated with apoptosis, cell cycle and endoplasmic reticulum (ER) stress were analyzed by western blotting.Results: PLK4 was overexpressed in AML cells. PLK4 knockdown or its specific inhibition by centrinone induced G2/M phase arrest via suppressing the expression of cyclin B1 and Cdc2 and promoting the level of proapoptotic proteins. Moreover, PLK4 targeting enhanced the level of proteins related to ER stress, such as GRP78, ATF4, ATF6, and CHOP.Conclusion: These findings demonstrated that targeting PLK4 can induce apoptosis, G2/M and ER stress in AML cells."

基金机构：National Natural Science Foundation of China [81772280]; Key Technology Innovation Special of Key Industries of the Chongqing Science and Technology Bureau [csct2022ycjh-bgzxm0034]

基金资助正文：Acknowledgements This work was supported by grants from the National Natural Science Foundation of China (Grant Number 81772280) and Key Technology Innovation Special of Key Industries of the Chongqing Science and Technology Bureau (Grant Number csct2022ycjh-bgzxm0034) .