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Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia

The prognosis of chemoresistant acute myeloid leukemia (AML) is still poor, mainly owing to the sustained proliferation ability of leukemic cells, while the microtubules have a major role in sustaining the continuity of cell cycle. In the present study, we have identified CENPE, a microtubular kines...

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Autores principales: Shi, Mingyue, Niu, Junwei, Niu, Xiaona, Guo, Honggang, Bai, Yanliang, Shi, Jie, Li, Weiya, Sun, Kai, Chen, Yuqing, Shao, Fengmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632764/
https://www.ncbi.nlm.nih.gov/pubmed/34868981
http://dx.doi.org/10.3389/fonc.2021.763232
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author Shi, Mingyue
Niu, Junwei
Niu, Xiaona
Guo, Honggang
Bai, Yanliang
Shi, Jie
Li, Weiya
Sun, Kai
Chen, Yuqing
Shao, Fengmin
author_facet Shi, Mingyue
Niu, Junwei
Niu, Xiaona
Guo, Honggang
Bai, Yanliang
Shi, Jie
Li, Weiya
Sun, Kai
Chen, Yuqing
Shao, Fengmin
author_sort Shi, Mingyue
collection PubMed
description The prognosis of chemoresistant acute myeloid leukemia (AML) is still poor, mainly owing to the sustained proliferation ability of leukemic cells, while the microtubules have a major role in sustaining the continuity of cell cycle. In the present study, we have identified CENPE, a microtubular kinesin-like motor protein that is highly expressed in the peripheral blood of patients with chemoresistant AML. In our in vitro studies, knockdown of CENPE expression resulted in the suppression of proliferation of myeloid leukemia cells and reversal of cytarabine (Ara-C) chemoresistance. Furthermore, Lin28A, one of the RNA-binding oncogene proteins that increase cell proliferation and invasion and contribute to unfavorable treatment responses in certain malignancies, was found to be remarkably correlated with CENPE expression in chemoresistance AML. Overexpression of LIN28A promoted the proliferation and Ara-C chemoresistance of leukemic cells. RIP assay, RNA pull-down, and dual luciferase reporter analyses indicated that LIN28A bound specifically to the promoter region GGAGA of CENPE. In addition, the impacts of LIN28A on cell growth, apoptosis, cell cycle progression, and Ara-C chemoresistance were reverted by the knockdown of CENPE. Hence, Lin28A/CENPE has enhanced the proliferation and chemoresistance of AML, and therefore, it could be a prospective candidate for AML treatment.
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spelling pubmed-86327642021-12-02 Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia Shi, Mingyue Niu, Junwei Niu, Xiaona Guo, Honggang Bai, Yanliang Shi, Jie Li, Weiya Sun, Kai Chen, Yuqing Shao, Fengmin Front Oncol Oncology The prognosis of chemoresistant acute myeloid leukemia (AML) is still poor, mainly owing to the sustained proliferation ability of leukemic cells, while the microtubules have a major role in sustaining the continuity of cell cycle. In the present study, we have identified CENPE, a microtubular kinesin-like motor protein that is highly expressed in the peripheral blood of patients with chemoresistant AML. In our in vitro studies, knockdown of CENPE expression resulted in the suppression of proliferation of myeloid leukemia cells and reversal of cytarabine (Ara-C) chemoresistance. Furthermore, Lin28A, one of the RNA-binding oncogene proteins that increase cell proliferation and invasion and contribute to unfavorable treatment responses in certain malignancies, was found to be remarkably correlated with CENPE expression in chemoresistance AML. Overexpression of LIN28A promoted the proliferation and Ara-C chemoresistance of leukemic cells. RIP assay, RNA pull-down, and dual luciferase reporter analyses indicated that LIN28A bound specifically to the promoter region GGAGA of CENPE. In addition, the impacts of LIN28A on cell growth, apoptosis, cell cycle progression, and Ara-C chemoresistance were reverted by the knockdown of CENPE. Hence, Lin28A/CENPE has enhanced the proliferation and chemoresistance of AML, and therefore, it could be a prospective candidate for AML treatment. Frontiers Media S.A. 2021-11-12 /pmc/articles/PMC8632764/ /pubmed/34868981 http://dx.doi.org/10.3389/fonc.2021.763232 Text en Copyright © 2021 Shi, Niu, Niu, Guo, Bai, Shi, Li, Sun, Chen and Shao 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 Oncology
Shi, Mingyue
Niu, Junwei
Niu, Xiaona
Guo, Honggang
Bai, Yanliang
Shi, Jie
Li, Weiya
Sun, Kai
Chen, Yuqing
Shao, Fengmin
Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
title Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
title_full Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
title_fullStr Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
title_full_unstemmed Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
title_short Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
title_sort lin28a/cenpe promoting the proliferation and chemoresistance of acute myeloid leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632764/
https://www.ncbi.nlm.nih.gov/pubmed/34868981
http://dx.doi.org/10.3389/fonc.2021.763232
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