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与Runt相关的转录因子2影响B细胞非霍奇金淋巴瘤和多发性骨髓瘤中细胞黏附介导的耐药性及细胞增殖。

Runt-related transcription factor 2 influences cell adhesion-mediated drug resistance and cell proliferation in B-cell non-Hodgkin's lymphoma and multiple myeloma.

作者信息

Zhang Pei-Pei, Wang Yu-Chan, Cheng Chun, Zhang Fei, Ding Da-Zhi, Chen Da-Ke

机构信息

Department of Oncology, Tongzhou District People's Hospital, Nantong, Jiangsu, 226000, People's Republic of China.

Department of Pathogenic Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.

出版信息

Leuk Res. 2020 May;92:106340. doi: 10.1016/j.leukres.2020.106340. Epub 2020 Mar 9.

Abstract

Several lines of evidence show that RUNX2 as a transcription factor is closely involved in carcinogenesis in a variety of human cancers. Cell adhesion-mediated drug resistance (CAM-DR) is an important part of the mechanism underlying drug resistance in hematological tumors. In this study, we investigated the biological function of RUNX2 in B-cell Non-Hodgkin's lymphoma (B-NHL) and multiple myeloma (MM). We assessed the expression of RUNX2 in suspension and adhesion model by western blot in B-NHL and MM. Adhesion assay, flow cytometry and CCK-8 were utilized to examine the role and mechanism of RUNX2 in CAM-DR and proliferation in B-NHL and MM. RUNX2 was highly expressed in adherent B-NHL and MM cells compared to suspension cells, and knockdown the expression of RUNX2 could reverse CAM-DR. Besides, RUNX2 could promote the proliferation of B-NHL and MM cells. Furthermore, RUNX2 participated the process of CAM-DR and proliferation by regulating the AKT/GSK-3β pathway. Developing RUNX2 inhibitor may be a possible strategy for drug resistance.

摘要

多项证据表明,RUNX2作为一种转录因子,与多种人类癌症的致癌作用密切相关。细胞黏附介导的耐药性(CAM-DR)是血液系统肿瘤耐药机制的重要组成部分。在本研究中,我们调查了RUNX2在B细胞非霍奇金淋巴瘤(B-NHL)和多发性骨髓瘤(MM)中的生物学功能。我们通过蛋白质免疫印迹法评估了RUNX2在B-NHL和MM悬浮及黏附模型中的表达。采用黏附试验、流式细胞术和CCK-8检测RUNX2在B-NHL和MM的CAM-DR及增殖中的作用和机制。与悬浮细胞相比,RUNX2在贴壁的B-NHL和MM细胞中高表达,敲低RUNX2的表达可逆转CAM-DR。此外,RUNX2可促进B-NHL和MM细胞的增殖。此外,RUNX2通过调节AKT/GSK-3β信号通路参与CAM-DR和增殖过程。开发RUNX2抑制剂可能是一种应对耐药性的策略。

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