ATP-binding cassette sub-family C member 4 (ABCC4) is overexpressed in human NK/T-cell lymphoma and regulates chemotherapy sensitivity: Potential as a functional therapeutic target
ATP-binding cassette sub-family C member 4 (ABCC4) is overexpressed in human NK/T-cell lymphoma and regulates chemotherapy sensitivity: Potential as a functional therapeutic target
复制标题
ATP 结合盒亚家族 C 成员 4 (ABCC4) 在人 NK/T 细胞淋巴瘤中过表达并调节化疗敏感性：有可能作为功能性治疗靶点。
DOI：
10.1016/j.leukres.2015.10.001
复制
发表时间：
2015-12-01
影响因子：
2.7
通讯作者：
Zhang, Mingzhi
中科院分区：
文献类型：
--
作者：
Zhang, Xudong;Zhao, Lu;Zhang, Mingzhi
Nasal-type natural killer/T-cell (NK/T-cell) lymphomas are subtypes of non-Hodgkin's lymphoma (NHL), which are typically more clinically aggressive. There is, however relatively little understanding of nasaltype NK/T-cell lymphoma molecular pathogenesis. Thus, in this study we applied RNA sequencing to systematically screen for altered gene expression in human NK/T-cell lymphoma cell lines YTS and SNK6 versus normal NK cells. We found that ATP-binding cassette sub-family C Member 4 (ABCC4) levels were significantly upregulated both in human NK/T-cell lymphoma YTS and SNK-6 cells, as compared with normal NK cells. These expression levels were further confirmed by real-time PCR. Protein levels of ABCC4 were also significantly higher in YTS and SNK-6 cells as compared with normal NK cells. Clinically relevant, ABCC4 expression levels were significantly higher in human NK/T-cell lymphoma tissues as compared with control nasal mucosa tissues, confirmed by immunohistochemical staining. In addition, we explored the biological function of such ABCC4 upregulation. Overexpression of ABCC4 by lentivirus transfection induced chemotherapy resistance to epirubicin (EPI) and cisplatin (DDP) in YTS cells. In contrast, knockdown of ABCC4 expression by shRNA contributed to chemotherapy sensitivity by both EPI and DDP. Furthermore, overexpression of ABCC4 inhibited, while downregulation of ABCC4 increased, YTS cell apoptosis following treatment by EPI or DDP. Therefore, the present study identified ABCC4 to be overexpressed in human NK/T-cell lymphoma cells, to regulate chemotherapy sensitivity to EPI and DDP, and possibly to be a functional therapeutic target. These findings may provide a basic rationale for new approaches in the effort to develop anti-tumor therapeutics for NK/T-cell lymphoma. (C) 2015 Elsevier Ltd. All rights reserved.
