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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Elsevier
2025-02-01
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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. |
format | Article |
id | doaj-art-0f7a33dc0e87421f983f66fa58321d9f |
institution | Kabale University |
issn | 2589-0042 |
language | English |
publishDate | 2025-02-01 |
publisher | Elsevier |
record_format | Article |
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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