Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51

Abstract Nucleolar and spindle-associated protein 1 (NUSAP1) is an essential regulator of mitotic progression, spindle assembly, and chromosome attachment. Although NUSAP1 acts as an oncogene involved in the progression of several cancers, the exact role of chronic lymphocytic leukemia (CLL) remains...

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Autores principales:	Yang Han, Xinting Hu, Xiaoya Yun, Jiarui Liu, Juan Yang, Zheng Tian, Xin Zhang, Ya Zhang, Xin Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/ee84516247dc42ed834e4a7ce073c5ad
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spelling	oai:doaj.org-article:ee84516247dc42ed834e4a7ce073c5ad2021-11-21T12:03:20ZNucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD5110.1038/s41419-021-04368-22041-4889https://doaj.org/article/ee84516247dc42ed834e4a7ce073c5ad2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04368-2https://doaj.org/toc/2041-4889Abstract Nucleolar and spindle-associated protein 1 (NUSAP1) is an essential regulator of mitotic progression, spindle assembly, and chromosome attachment. Although NUSAP1 acts as an oncogene involved in the progression of several cancers, the exact role of chronic lymphocytic leukemia (CLL) remains elusive. Herein, we first discovered obvious overexpression of NUSAP1 in CLL associated with poor prognosis. Next, the NUSAP1 level was modulated by transfecting CLL cells with lentivirus. Silencing NUSAP1 inhibited the cell proliferation, promoted cell apoptosis and G0/G1 phase arrest. Mechanistically, high expression of NUSAP1 strengthened DNA damage repairing with RAD51 engagement. Our results also indicated that NUSAP1 knockdown suppressed the growth CLL cells in vivo. We further confirmed that NUSAP1 reduction enhanced the sensitivity of CLL cells to fludarabine or ibrutinib. Overall, our research investigates the mechanism by which NUSAP1 enhances chemoresistance via DNA damage repair (DDR) signaling by stabilizing RAD51 in CLL cells. Hence, NUSAP1 may be expected to be a perspective target for the treatment of CLL with chemotherapy resistance.Yang HanXinting HuXiaoya YunJiarui LiuJuan YangZheng TianXin ZhangYa ZhangXin WangNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Yang Han Xinting Hu Xiaoya Yun Jiarui Liu Juan Yang Zheng Tian Xin Zhang Ya Zhang Xin Wang Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51
description	Abstract Nucleolar and spindle-associated protein 1 (NUSAP1) is an essential regulator of mitotic progression, spindle assembly, and chromosome attachment. Although NUSAP1 acts as an oncogene involved in the progression of several cancers, the exact role of chronic lymphocytic leukemia (CLL) remains elusive. Herein, we first discovered obvious overexpression of NUSAP1 in CLL associated with poor prognosis. Next, the NUSAP1 level was modulated by transfecting CLL cells with lentivirus. Silencing NUSAP1 inhibited the cell proliferation, promoted cell apoptosis and G0/G1 phase arrest. Mechanistically, high expression of NUSAP1 strengthened DNA damage repairing with RAD51 engagement. Our results also indicated that NUSAP1 knockdown suppressed the growth CLL cells in vivo. We further confirmed that NUSAP1 reduction enhanced the sensitivity of CLL cells to fludarabine or ibrutinib. Overall, our research investigates the mechanism by which NUSAP1 enhances chemoresistance via DNA damage repair (DDR) signaling by stabilizing RAD51 in CLL cells. Hence, NUSAP1 may be expected to be a perspective target for the treatment of CLL with chemotherapy resistance.
format	article
author	Yang Han Xinting Hu Xiaoya Yun Jiarui Liu Juan Yang Zheng Tian Xin Zhang Ya Zhang Xin Wang
author_facet	Yang Han Xinting Hu Xiaoya Yun Jiarui Liu Juan Yang Zheng Tian Xin Zhang Ya Zhang Xin Wang
author_sort	Yang Han
title	Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51
title_short	Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51
title_full	Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51
title_fullStr	Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51
title_full_unstemmed	Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51
title_sort	nucleolar and spindle associated protein 1 enhances chemoresistance through dna damage repair pathway in chronic lymphocytic leukemia by binding with rad51
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/ee84516247dc42ed834e4a7ce073c5ad
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_version_	1718419338682171392

Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51

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