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:	Mingyue Shi, Junwei Niu, Xiaona Niu, Honggang Guo, Yanliang Bai, Jie Shi, Weiya Li, Kai Sun, Yuqing Chen, Fengmin Shao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	CENPE LIN28A AML chemoresistance cell cycle Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/cfa642e22dfe4ac6b60f058668cc5dd0
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spelling	oai:doaj.org-article:cfa642e22dfe4ac6b60f058668cc5dd02021-11-12T04:57:30ZLin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia2234-943X10.3389/fonc.2021.763232https://doaj.org/article/cfa642e22dfe4ac6b60f058668cc5dd02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.763232/fullhttps://doaj.org/toc/2234-943XThe 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.Mingyue ShiJunwei NiuXiaona NiuHonggang GuoYanliang BaiJie ShiWeiya LiKai SunYuqing ChenFengmin ShaoFrontiers Media S.A.articleCENPELIN28AAMLchemoresistancecell cycleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CENPE LIN28A AML chemoresistance cell cycle Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	CENPE LIN28A AML chemoresistance cell cycle Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mingyue Shi Junwei Niu Xiaona Niu Honggang Guo Yanliang Bai Jie Shi Weiya Li Kai Sun Yuqing Chen Fengmin Shao Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
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.
format	article
author	Mingyue Shi Junwei Niu Xiaona Niu Honggang Guo Yanliang Bai Jie Shi Weiya Li Kai Sun Yuqing Chen Fengmin Shao
author_facet	Mingyue Shi Junwei Niu Xiaona Niu Honggang Guo Yanliang Bai Jie Shi Weiya Li Kai Sun Yuqing Chen Fengmin Shao
author_sort	Mingyue Shi
title	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_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_sort	lin28a/cenpe promoting the proliferation and chemoresistance of acute myeloid leukemia
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cfa642e22dfe4ac6b60f058668cc5dd0
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Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia

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