Abstract:
: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 nasal-type 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 SNK-6 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.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Zhang X,Zhao L,Li X,Wang X,Li L,Fu X,Sun Z,Li Z,Nan F,Chang Y,Zhang Mdoi
10.1016/j.leukres.2015.10.001subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1448-54issue
12eissn
0145-2126issn
1873-5835pii
S0145-2126(15)30393-3journal_volume
39pub_type
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journal_title:Leukemia research
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journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
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journal_title:Leukemia research
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pub_type: 杂志文章
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journal_title:Leukemia research
pub_type: 杂志文章
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