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Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines
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 u...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424683/ https://www.ncbi.nlm.nih.gov/pubmed/36051696 http://dx.doi.org/10.3389/fgene.2022.898474 |
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author | 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 |
author_facet | 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 |
author_sort | Mu, Xing-Ru |
collection | PubMed |
description | 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 via 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 in vitro, and these results herein may provide clues in roles of PLK4 in the leukemiagenesis of AML. |
format | Online Article Text |
id | pubmed-9424683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94246832022-08-31 Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines 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 Front Genet Genetics 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 via 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 in vitro, and these results herein may provide clues in roles of PLK4 in the leukemiagenesis of AML. Frontiers Media S.A. 2022-08-16 /pmc/articles/PMC9424683/ /pubmed/36051696 http://dx.doi.org/10.3389/fgene.2022.898474 Text en Copyright © 2022 Mu, Ma, Lu, Liu, Xue, Cao, Zeng, Li, Xu and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics 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 Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines |
title | Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines |
title_full | Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines |
title_fullStr | Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines |
title_full_unstemmed | Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines |
title_short | Effects of the PLK4 inhibitor Centrinone on the biological behaviors of acute myeloid leukemia cell lines |
title_sort | effects of the plk4 inhibitor centrinone on the biological behaviors of acute myeloid leukemia cell lines |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424683/ https://www.ncbi.nlm.nih.gov/pubmed/36051696 http://dx.doi.org/10.3389/fgene.2022.898474 |
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