ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibition

Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, with poor prognosis due to late diagnosis and limited treatment options. In this study, we evaluated the expression of ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in HCC tissues and its clinic...

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Main Authors: Si-qi Zhao, Min-jie Chen, Fei Chen, Zhao-feng Gao, Xiao-ping Li, Ling-yu Hu, Hai-ying Cheng, Jin-yan Xuan, Jian-guo Fei, Zheng-wei Song
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225000793
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author Si-qi Zhao
Min-jie Chen
Fei Chen
Zhao-feng Gao
Xiao-ping Li
Ling-yu Hu
Hai-ying Cheng
Jin-yan Xuan
Jian-guo Fei
Zheng-wei Song
author_facet Si-qi Zhao
Min-jie Chen
Fei Chen
Zhao-feng Gao
Xiao-ping Li
Ling-yu Hu
Hai-ying Cheng
Jin-yan Xuan
Jian-guo Fei
Zheng-wei Song
author_sort Si-qi Zhao
collection DOAJ
description Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, with poor prognosis due to late diagnosis and limited treatment options. In this study, we evaluated the expression of ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in HCC tissues and its clinical significance. Immunohistochemistry, The Cancer Genome Atlas (TCGA) data, and single-cell expression analysis revealed reduced ENTPD8 levels in liver cancer compared to adjacent tissues, with ENTPD8 primarily expressed in tumor cells within the tumor tissue. In vitro assays demonstrated that ENTPD8 inhibits HCC cell proliferation, invasion, and migration. Mechanistically, ENTPD8 regulates programmed death-ligand 1 (PD-L1) expression through miR-214-5p modulation. In vivo, ENTPD8 overexpression combined with anti-PD-L1 treatment enhanced therapeutic efficacy in HCC mouse models. These findings suggest that ENTPD8 may serve as a prognostic marker and therapeutic target for HCC, offering potential strategies for improving treatment outcomes.
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institution Kabale University
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publishDate 2025-02-01
publisher Elsevier
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series iScience
spelling doaj-art-0f7a33dc0e87421f983f66fa58321d9f2025-02-10T04:34:44ZengElsevieriScience2589-00422025-02-01282111819ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibitionSi-qi Zhao0Min-jie Chen1Fei Chen2Zhao-feng Gao3Xiao-ping Li4Ling-yu Hu5Hai-ying Cheng6Jin-yan Xuan7Jian-guo Fei8Zheng-wei Song9Department of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, ChinaDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, ChinaDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, ChinaDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, ChinaDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, ChinaDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, ChinaDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, ChinaDepartment of General Practice, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China; Corresponding authorDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China; Corresponding authorDepartment of Surgery, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China; Corresponding authorSummary: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, with poor prognosis due to late diagnosis and limited treatment options. In this study, we evaluated the expression of ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in HCC tissues and its clinical significance. Immunohistochemistry, The Cancer Genome Atlas (TCGA) data, and single-cell expression analysis revealed reduced ENTPD8 levels in liver cancer compared to adjacent tissues, with ENTPD8 primarily expressed in tumor cells within the tumor tissue. In vitro assays demonstrated that ENTPD8 inhibits HCC cell proliferation, invasion, and migration. Mechanistically, ENTPD8 regulates programmed death-ligand 1 (PD-L1) expression through miR-214-5p modulation. In vivo, ENTPD8 overexpression combined with anti-PD-L1 treatment enhanced therapeutic efficacy in HCC mouse models. These findings suggest that ENTPD8 may serve as a prognostic marker and therapeutic target for HCC, offering potential strategies for improving treatment outcomes.http://www.sciencedirect.com/science/article/pii/S2589004225000793molecular biologycell biologycancer
spellingShingle Si-qi Zhao
Min-jie Chen
Fei Chen
Zhao-feng Gao
Xiao-ping Li
Ling-yu Hu
Hai-ying Cheng
Jin-yan Xuan
Jian-guo Fei
Zheng-wei Song
ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibition
iScience
molecular biology
cell biology
cancer
title ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibition
title_full ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibition
title_fullStr ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibition
title_full_unstemmed ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibition
title_short ENTPD8 overexpression enhances anti-PD-L1 therapy in hepatocellular carcinoma via miR-214-5p inhibition
title_sort entpd8 overexpression enhances anti pd l1 therapy in hepatocellular carcinoma via mir 214 5p inhibition
topic molecular biology
cell biology
cancer
url http://www.sciencedirect.com/science/article/pii/S2589004225000793
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