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PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia

BACKGROUND: Prickle planar cell polarity protein 1 (PRICKLE1), a core component of the non-canonical Wnt/planar cell polarity (PCP) pathway, was recently reported to be upregulated and correlated with poor prognosis in solid cancers. However, the effect of PRICKLE1 on acute myeloid leukemia (AML) re...

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Autores principales: Jiang, Duanfeng, He, Yanjuan, Mo, Qiuyu, Liu, Enyi, Li, Xin, Huang, Lihua, Zhang, Qin, Chen, Fangping, Li, Yan, Shao, Haigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130533/
https://www.ncbi.nlm.nih.gov/pubmed/34001134
http://dx.doi.org/10.1186/s12967-021-02873-8
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author Jiang, Duanfeng
He, Yanjuan
Mo, Qiuyu
Liu, Enyi
Li, Xin
Huang, Lihua
Zhang, Qin
Chen, Fangping
Li, Yan
Shao, Haigang
author_facet Jiang, Duanfeng
He, Yanjuan
Mo, Qiuyu
Liu, Enyi
Li, Xin
Huang, Lihua
Zhang, Qin
Chen, Fangping
Li, Yan
Shao, Haigang
author_sort Jiang, Duanfeng
collection PubMed
description BACKGROUND: Prickle planar cell polarity protein 1 (PRICKLE1), a core component of the non-canonical Wnt/planar cell polarity (PCP) pathway, was recently reported to be upregulated and correlated with poor prognosis in solid cancers. However, the effect of PRICKLE1 on acute myeloid leukemia (AML) remains unknown. This study aims to characterize the prognostic significance of PRICKLE1 expression in patients with AML. METHODS: RNA-seq was performed to compare mRNA expression profiles of AML patients and healthy controls. qRT-PCR and western blotting were used to analyze the expression of PRICKLE1 in AML patients and cell lines, and two independent datasets (TCGA-LAML and TARGET-AML) online were used to validate the expression results. The correlations between the expression of PRICKLE1 and clinical features were further analyzed. RESULTS: Our data showed that PRICKLE1 expression levels were markedly high in AML patients at the time of diagnosis, decreased after complete remission and increased again at relapse. Of note, PRICKLE1 was highly expressed in drug resistant AML cells and monocytic-AML patients. High PRICKLE1 expression was found in FLT3/DNMT3A/IDH1/IDH2-mutant AML and associated with poor prognosis. Furthermore, high expression of PRICKLE1 may be correlated with migration and invasion components upregulation in AML patients. CONCLUSIONS: These results indicated that high PRICKLE1 expression may be a poor prognostic biomarker and therapeutic target of AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02873-8.
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spelling pubmed-81305332021-05-19 PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia Jiang, Duanfeng He, Yanjuan Mo, Qiuyu Liu, Enyi Li, Xin Huang, Lihua Zhang, Qin Chen, Fangping Li, Yan Shao, Haigang J Transl Med Research BACKGROUND: Prickle planar cell polarity protein 1 (PRICKLE1), a core component of the non-canonical Wnt/planar cell polarity (PCP) pathway, was recently reported to be upregulated and correlated with poor prognosis in solid cancers. However, the effect of PRICKLE1 on acute myeloid leukemia (AML) remains unknown. This study aims to characterize the prognostic significance of PRICKLE1 expression in patients with AML. METHODS: RNA-seq was performed to compare mRNA expression profiles of AML patients and healthy controls. qRT-PCR and western blotting were used to analyze the expression of PRICKLE1 in AML patients and cell lines, and two independent datasets (TCGA-LAML and TARGET-AML) online were used to validate the expression results. The correlations between the expression of PRICKLE1 and clinical features were further analyzed. RESULTS: Our data showed that PRICKLE1 expression levels were markedly high in AML patients at the time of diagnosis, decreased after complete remission and increased again at relapse. Of note, PRICKLE1 was highly expressed in drug resistant AML cells and monocytic-AML patients. High PRICKLE1 expression was found in FLT3/DNMT3A/IDH1/IDH2-mutant AML and associated with poor prognosis. Furthermore, high expression of PRICKLE1 may be correlated with migration and invasion components upregulation in AML patients. CONCLUSIONS: These results indicated that high PRICKLE1 expression may be a poor prognostic biomarker and therapeutic target of AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02873-8. BioMed Central 2021-05-17 /pmc/articles/PMC8130533/ /pubmed/34001134 http://dx.doi.org/10.1186/s12967-021-02873-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jiang, Duanfeng
He, Yanjuan
Mo, Qiuyu
Liu, Enyi
Li, Xin
Huang, Lihua
Zhang, Qin
Chen, Fangping
Li, Yan
Shao, Haigang
PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
title PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
title_full PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
title_fullStr PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
title_full_unstemmed PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
title_short PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
title_sort prickle1, a wnt/pcp signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130533/
https://www.ncbi.nlm.nih.gov/pubmed/34001134
http://dx.doi.org/10.1186/s12967-021-02873-8
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