2. Academic Validation
  3. Downregulation of Polo-like kinase 4 induces cell apoptosis and G2/M arrest in acute myeloid leukemia

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

  • Pathol Res Pract. 2023 Feb 12;243:154376. doi: 10.1016/j.prp.2023.154376.
Shuyu Chen 1,  Liang Zhong 2,  Xuan Chu 1,  Peng Wan 1,  Zhenyan Liu 1,  Yang Lu 1,  Zhonghui Zhang 1,  Xiao Wang 1,  Ziwei Zhou 1,  Xin Shao 1,  Beizhong Liu 3
Affiliations

Affiliations

  • 1 Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
  • 2 Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
  • 3 Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China; Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
PMID: 36821942 DOI: 10.1016/j.prp.2023.154376
Abstract

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.

Keywords

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

Figures
Products