Nucleolar and spindle associated protein 1 enhances chemoresistance through DNA damage repair pathway in chronic lymphocytic leukemia by binding with RAD51.
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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DOI：
10.1038/s41419-021-04368-2
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发表时间：
2021-11-15
影响因子：
9
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Han Y;Hu X;Yun X;Liu J;Yang J;Tian Z;Zhang X;Zhang Y;Wang X
核仁和纺锤体相关蛋白1（NUSAP 1）是有丝分裂进程、纺锤体组装和染色体附着的重要调节因子。尽管NUSAP 1作为一种致癌基因参与了几种癌症的进展，但慢性淋巴细胞白血病（CLL）的确切作用仍然难以捉摸。在此，我们首次发现NUSAP 1在CLL中的明显过表达与不良预后相关。接下来，通过用慢病毒转染CLL细胞来调节NUSAP 1水平。沉默NUSAP 1可抑制细胞增殖，促进细胞凋亡和G 0/G1期阻滞。从机制上讲，NUSAP 1的高表达加强了与RAD 51接合的DNA损伤修复。我们的研究结果还表明NUSAP 1敲低抑制CLL细胞在体内的生长。我们进一步证实NUSAP 1减少增强了CLL细胞对氟达拉滨或伊曲替尼的敏感性。总的来说，我们的研究调查了NUSAP 1通过稳定CLL细胞中的RAD 51通过DNA损伤修复（DDR）信号增强化学抗性的机制。因此，NUSAP 1有望成为治疗化疗耐药CLL的潜在靶点。
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.
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DOI：
10.1007/978-1-4939-8876-1_12
发表时间：
2019-01-01
期刊：
CHRONIC LYMPHOCYTIC LEUKEMIA
影响因子：
--
作者：
Lai, Tzung-Huei;Sampath, Deepa
通讯作者：
Sampath, Deepa
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
10.1
作者：
Boudny, Miroslav;Zemanova, Jana;Trbusek, Martin
通讯作者：
Trbusek, Martin
影响因子：
2.6
作者：
Lew, Thomas E.;Cheah, Chan Y.;Tam, Constantine S.
通讯作者：
Tam, Constantine S.
影响因子：
2.4
作者：
Izutsu K;Kinoshita T;Takizawa J;Fukuhara S;Yamamoto G;Ohashi Y;Suzumiya J;Tobinai K
通讯作者：
Tobinai K