Mu Xing-Ru, Ma Meng-Meng, Lu Zi-Yi, Liu Jun, Xue Yu-Tong, Cao Jiang, Zeng Ling-Yu, Li Feng, Xu Kai-Lin, Wu Qing-Yun
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Front Genet. 2022 Aug 16;13:898474. doi: 10.3389/fgene.2022.898474. eCollection 2022.
Polo-like kinase 4 (PLK4), a key regulator of centriole biogenesis, is frequently overexpressed in cancer cells. However, roles and the mechanism of PLK4 in the leukemiagenesis of acute myeloid leukemia (AML) remain unclear. In this study, the PLK4 inhibitor Centrinone and the shRNA knockdown were used to investigate roles and the mechanism of PLK4 in the leukemiagenesis of AML. Our results indicated that Centrinone inhibited the proliferation of AML cells in a dose- and time-dependent manner reduced the expression of PLK4 both in the protein and mRNA levels. Moreover, colony formation assay revealed that Centrinone reduced the number and the size of the AML colonies. Centrinone induced AML cell apoptosis by increasing the activation of Caspase-3/poly ADP-ribose polymerase (PARP). Notably, Centrinone caused the G2/M phase cell cycle arrest by decreasing the expression of cell cycle-related proteins such as Cyclin A2, Cyclin B1, and Cyclin-dependent kinase 1 (CDK1). Consistent with above results, knockdown the expression of PLK4 also inhibited cell proliferation and colony formation, induced cell apoptosis, and caused G2/M phase cell cycle arrest without affecting cell differentiation. All in all, this study suggested that PLK4 inhibited the progression of AML , and these results herein may provide clues in roles of PLK4 in the leukemiagenesis of AML.
Polo样激酶4（PLK4）是中心粒生物发生的关键调节因子，在癌细胞中经常过度表达。然而，PLK4在急性髓系白血病（AML）白血病发生中的作用和机制仍不清楚。在本研究中，使用PLK4抑制剂Centrinone和shRNA敲低技术来研究PLK4在AML白血病发生中的作用和机制。我们的结果表明，Centrinone以剂量和时间依赖性方式抑制AML细胞的增殖，在蛋白质和mRNA水平上均降低了PLK4的表达。此外，集落形成试验显示Centrinone减少了AML集落的数量和大小。Centrinone通过增加半胱天冬酶-3/聚ADP核糖聚合酶（PARP）的激活来诱导AML细胞凋亡。值得注意的是，Centrinone通过降低细胞周期相关蛋白如细胞周期蛋白A2、细胞周期蛋白B1和细胞周期蛋白依赖性激酶1（CDK1）的表达导致G2/M期细胞周期停滞。与上述结果一致，敲低PLK4的表达也抑制细胞增殖和集落形成，诱导细胞凋亡，并导致G2/M期细胞周期停滞，而不影响细胞分化。总而言之，本研究表明PLK4抑制AML的进展，本文的这些结果可能为PLK4在AML白血病发生中的作用提供线索。
