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DYRK2基因沉默可增加非霍奇金淋巴瘤细胞的增殖,但可逆转其多药耐药性。

Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin's Lymphoma.

作者信息

Wang Yuchan, Wu Yaxun, Miao Xiaobing, Zhu Xinghua, Miao Xianjing, He Yunhua, Zhong Fei, Ding Linlin, Liu Jing, Tang Jie, Huang Yuejiao, Xu Xiaohong, He Song

机构信息

Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu, China.

Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu, China.

出版信息

Int J Biol Macromol. 2015 Nov;81:809-17. doi: 10.1016/j.ijbiomac.2015.08.067. Epub 2015 Sep 2.

Abstract

DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation regulated kinase gene, is involved in regulating many processes such as cell proliferation, cell differentiation and cytokinesis. DYRK2 also plays an important role in many cancers, such as breast cancer, non-small cell lung cancer and esophageal adenocarcinomas. In this study, we found that DYRK2 is associated with the proliferation of Non-Hodgkin's lymphoma (NHL) and cell adhesion mediated drug resistance (CAM-DR). Clinically, the mRNA and protein expression levels of DYRK2 are decreased in NHL tissues compared with reactive lymphoid hyperplasia tissues. Immunohistochemical analysis revealed that low expression of DYRK2 is associated with poor prognosis of NHL patients. Interestingly, knockdown of DYRK2 can promote cell proliferation via modulating cell cycle progression. Finally, we demonstrated that DYRK2 plays an important role in CAM-DR by regulating p27(Kip1) expression. Importantly, DYRK2 knockdown reverses CAM-DR in NHL. Our research suggested that DYRK2 may be a novel therapeutic target for NHL.

摘要

DYRK2是一种双特异性酪氨酸(Y)磷酸化调节激酶基因,参与调节细胞增殖、细胞分化和胞质分裂等多种过程。DYRK2在许多癌症中也发挥着重要作用,如乳腺癌、非小细胞肺癌和食管腺癌。在本研究中,我们发现DYRK2与非霍奇金淋巴瘤(NHL)的增殖以及细胞黏附介导的耐药性(CAM-DR)相关。临床上,与反应性淋巴组织增生组织相比,NHL组织中DYRK2的mRNA和蛋白表达水平降低。免疫组织化学分析显示,DYRK2低表达与NHL患者的不良预后相关。有趣的是,敲低DYRK2可通过调节细胞周期进程促进细胞增殖。最后,我们证明DYRK2通过调节p27(Kip1)表达在CAM-DR中起重要作用。重要的是,敲低DYRK2可逆转NHL中的CAM-DR。我们的研究表明,DYRK2可能是NHL的一个新的治疗靶点。

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