miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular Carcinoma
Tumour vascular mimicry (VM) is the process by which new blood vessels are formed by tumour cells rather than endothelial cells. An increasing number of studies have revealed that the VM process is associated with cancer progression and metastasis. MiR-138-5p has been reported to act as a tumour sup...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/7318950 |
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| author | Hongwei Liu Tao Tang Xiujin Hu Weihe Tan Peng Zhou Huixian Zhang Yanmei Liu Chen Chen Meng Yang Meifang Zhou Shuxia Xuan Bin Cheng Weiguo Yin Jinduan Lin |
| author_facet | Hongwei Liu Tao Tang Xiujin Hu Weihe Tan Peng Zhou Huixian Zhang Yanmei Liu Chen Chen Meng Yang Meifang Zhou Shuxia Xuan Bin Cheng Weiguo Yin Jinduan Lin |
| author_sort | Hongwei Liu |
| collection | DOAJ |
| description | Tumour vascular mimicry (VM) is the process by which new blood vessels are formed by tumour cells rather than endothelial cells. An increasing number of studies have revealed that the VM process is associated with cancer progression and metastasis. MiR-138-5p has been reported to act as a tumour suppressor in many cancers. However, the role and underlying mechanism of miR-138-5p in hepatocellular carcinoma (HCC) VM remain unclear. In this study, VM density was detected by CD31/periodic acid-Schiff double staining in HCC clinical specimens. We found that miR-138-5p expression correlated strongly and negatively with microvessel density. Additionally, the miR-138-5p mimic or inhibitor decreased or increased, respectively, tube formation capacity in HepG2 and Hep3B cells. Consistent with this finding, miR-138-5p repressed vessel density in vivo. Moreover, miR-138-5p targeted hypoxia-inducible factor 1α (HIF-1α) and regulated the expression of HIF-1α and vascular endothelial growth factor A (VEGFA), which are established classical master regulators for angiogenesis. Consistent with these findings, the HIF-1α inhibitor CAY10585 effectively blocked HCC cell VM and VEGFA expression. In conclusion, miR-138-5p inhibits HepG2 and Hep3B cell VM by blocking the HIF-1α/VEGFA pathway. Therefore, miR-138-5p may serve as a useful therapeutic target for miRNA-based HCC therapy. |
| format | Article |
| id | doaj-art-79f3e26a4a5d455c9ff4b2cf6d46f55f |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-79f3e26a4a5d455c9ff4b2cf6d46f55f2025-08-20T03:35:48ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/7318950miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular CarcinomaHongwei Liu0Tao Tang1Xiujin Hu2Weihe Tan3Peng Zhou4Huixian Zhang5Yanmei Liu6Chen Chen7Meng Yang8Meifang Zhou9Shuxia Xuan10Bin Cheng11Weiguo Yin12Jinduan Lin13Department of Laboratory Medicine CenterDepartment of Molecular DiagnosticsDepartment of Hepatobiliary SurgeryDepartment of Obstetrics and GynecologyDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterDepartment of Laboratory Medicine CenterTumour vascular mimicry (VM) is the process by which new blood vessels are formed by tumour cells rather than endothelial cells. An increasing number of studies have revealed that the VM process is associated with cancer progression and metastasis. MiR-138-5p has been reported to act as a tumour suppressor in many cancers. However, the role and underlying mechanism of miR-138-5p in hepatocellular carcinoma (HCC) VM remain unclear. In this study, VM density was detected by CD31/periodic acid-Schiff double staining in HCC clinical specimens. We found that miR-138-5p expression correlated strongly and negatively with microvessel density. Additionally, the miR-138-5p mimic or inhibitor decreased or increased, respectively, tube formation capacity in HepG2 and Hep3B cells. Consistent with this finding, miR-138-5p repressed vessel density in vivo. Moreover, miR-138-5p targeted hypoxia-inducible factor 1α (HIF-1α) and regulated the expression of HIF-1α and vascular endothelial growth factor A (VEGFA), which are established classical master regulators for angiogenesis. Consistent with these findings, the HIF-1α inhibitor CAY10585 effectively blocked HCC cell VM and VEGFA expression. In conclusion, miR-138-5p inhibits HepG2 and Hep3B cell VM by blocking the HIF-1α/VEGFA pathway. Therefore, miR-138-5p may serve as a useful therapeutic target for miRNA-based HCC therapy.http://dx.doi.org/10.1155/2022/7318950 |
| spellingShingle | Hongwei Liu Tao Tang Xiujin Hu Weihe Tan Peng Zhou Huixian Zhang Yanmei Liu Chen Chen Meng Yang Meifang Zhou Shuxia Xuan Bin Cheng Weiguo Yin Jinduan Lin miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular Carcinoma Journal of Immunology Research |
| title | miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular Carcinoma |
| title_full | miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular Carcinoma |
| title_fullStr | miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular Carcinoma |
| title_full_unstemmed | miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular Carcinoma |
| title_short | miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1α/VEGFA Pathway in Hepatocellular Carcinoma |
| title_sort | mir 138 5p inhibits vascular mimicry by targeting the hif 1α vegfa pathway in hepatocellular carcinoma |
| url | http://dx.doi.org/10.1155/2022/7318950 |
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