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.
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.
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Xudong
X
Zhang
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Lu
L
Zhao
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Xin
X
Li
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Xinhua
X
Wang
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Ling
L
Li
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Xiaorui
X
Fu
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Zhenchang
Z
Sun
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Zhaoming
Z
Li
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Feifei
F
Nan
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China.
Yu
Y
Chang
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan, China. Electronic address: mingzhi_zhang1@126.com.
Mingzhi
M
Zhang
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology*; D015251:Epirubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D054391:Lymphoma, Extranodal NK-T-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058990:Molecular Targeted Therapy; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009297:Nasal Mucosa / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009669:Nose Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014161:Transduction, Genetic
D002945:Cisplatin; D015251:Epirubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C073492:ABCC4 protein, human
ABCC4; Cisplatin; Epirubicin; NK/T-cell lymphoma