Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma
Abstract Background Angiogenesis is considered as an important process in the development of malignancies and is associated with cancer progression and metastasis. Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is recognized as a typical angiogenic tumor. Thus, it i...
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0727-1 |
| _version_ | 1818925903940419584 |
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| author | Jinduan Lin Shunwang Cao Yu Wang Yanwei Hu Hongwei Liu Jiehua Li Jing Chen Pan Li Jumei Liu Qian Wang Lei Zheng |
| author_facet | Jinduan Lin Shunwang Cao Yu Wang Yanwei Hu Hongwei Liu Jiehua Li Jing Chen Pan Li Jumei Liu Qian Wang Lei Zheng |
| author_sort | Jinduan Lin |
| collection | DOAJ |
| description | Abstract Background Angiogenesis is considered as an important process in the development of malignancies and is associated with cancer progression and metastasis. Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is recognized as a typical angiogenic tumor. Thus, it is of great importance to study the underlying mechanism of angiogenesis in HCC. The long non-coding RNA (lncRNA) ubiquitin conjugating enzyme E2C pseudogene 3 (UBE2CP3) has been reported as an oncogene that promotes tumor metastasis in HCC. However, the role and underlying mechanisms of UBE2CP3 in HCC angiogenesis are still unclear. Methods We measured the expression levels of UBE2CP3 by in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in HCC patient samples. We also concomitantly used CD31/PAS double-staining to measure endothelial vessel (EV) density and used qRT-PCR to measure the CD31 mRNA level. HepG2 and SMMC-7721 cells were transfected with Lv-UBE2CP3 or Sh-UBE2CP3 virus to obtain stably over-expressing or knocking-down UBE2CP3 cell lines. The indirect effects of UBE2CP3 on ECs were studied by establishing a co-culture system using Transwell chambers with a 0.4-μm pore size. HCC cells and ECs in the co-culture system were separated, but the cytokines and growth factors were able to communicate with each other. Following exposed to HCC cells, ECs were collected for functional studies. Finally, we studied the function of UBE2CP3 in vivo by chick embryo chorioallantoic membrane (CAM) angiogenesis assays and nude mouse tumorigenicity assays. Results In this study, we found that UBE2CP3 expression was higher in HCC tissues than in para-tumor tissues and was up-regulated in tissues with high EV density. Functionally, we found that in the co-culture systems, HCC cells overexpressing UBE2CP3 promoted HUVEC proliferation, migration and tube formation via the activation of ERK/HIF-1α/p70S6K/VEGFA signalling, increasing the level of VEGFA in HCC cell supernatant. In addition, the opposite results appeared when the expression of UBE2CP3 in HCC cells was knocked down. Consistent with these results, CAM angiogenesis assays and nude mouse tumorigenicity assays showed that UBE2CP3 expression up-regulated EV density in vivo. Conclusion Our study suggests that UBE2CP3 can enhance the interaction between HCC tumor cells and HUVECs and promote HCC tumorigenicity by facilitating angiogenesis. |
| first_indexed | 2024-12-20T02:48:38Z |
| format | Article |
| id | doaj.art-85cfb66ecdc040f49ac5c0c1c2a69386 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-20T02:48:38Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-85cfb66ecdc040f49ac5c0c1c2a693862022-12-21T19:56:06ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-06-0137111310.1186/s13046-018-0727-1Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinomaJinduan Lin0Shunwang Cao1Yu Wang2Yanwei Hu3Hongwei Liu4Jiehua Li5Jing Chen6Pan Li7Jumei Liu8Qian Wang9Lei Zheng10Department of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Clinical Laboratory, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Clinical Laboratory, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityDepartment of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical UniversityAbstract Background Angiogenesis is considered as an important process in the development of malignancies and is associated with cancer progression and metastasis. Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is recognized as a typical angiogenic tumor. Thus, it is of great importance to study the underlying mechanism of angiogenesis in HCC. The long non-coding RNA (lncRNA) ubiquitin conjugating enzyme E2C pseudogene 3 (UBE2CP3) has been reported as an oncogene that promotes tumor metastasis in HCC. However, the role and underlying mechanisms of UBE2CP3 in HCC angiogenesis are still unclear. Methods We measured the expression levels of UBE2CP3 by in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in HCC patient samples. We also concomitantly used CD31/PAS double-staining to measure endothelial vessel (EV) density and used qRT-PCR to measure the CD31 mRNA level. HepG2 and SMMC-7721 cells were transfected with Lv-UBE2CP3 or Sh-UBE2CP3 virus to obtain stably over-expressing or knocking-down UBE2CP3 cell lines. The indirect effects of UBE2CP3 on ECs were studied by establishing a co-culture system using Transwell chambers with a 0.4-μm pore size. HCC cells and ECs in the co-culture system were separated, but the cytokines and growth factors were able to communicate with each other. Following exposed to HCC cells, ECs were collected for functional studies. Finally, we studied the function of UBE2CP3 in vivo by chick embryo chorioallantoic membrane (CAM) angiogenesis assays and nude mouse tumorigenicity assays. Results In this study, we found that UBE2CP3 expression was higher in HCC tissues than in para-tumor tissues and was up-regulated in tissues with high EV density. Functionally, we found that in the co-culture systems, HCC cells overexpressing UBE2CP3 promoted HUVEC proliferation, migration and tube formation via the activation of ERK/HIF-1α/p70S6K/VEGFA signalling, increasing the level of VEGFA in HCC cell supernatant. In addition, the opposite results appeared when the expression of UBE2CP3 in HCC cells was knocked down. Consistent with these results, CAM angiogenesis assays and nude mouse tumorigenicity assays showed that UBE2CP3 expression up-regulated EV density in vivo. Conclusion Our study suggests that UBE2CP3 can enhance the interaction between HCC tumor cells and HUVECs and promote HCC tumorigenicity by facilitating angiogenesis.http://link.springer.com/article/10.1186/s13046-018-0727-1Long non-coding RNA, UBE2CP3, HCC, Angiogenesis, ERK, VEGFA, Co-culture |
| spellingShingle | Jinduan Lin Shunwang Cao Yu Wang Yanwei Hu Hongwei Liu Jiehua Li Jing Chen Pan Li Jumei Liu Qian Wang Lei Zheng Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma Journal of Experimental & Clinical Cancer Research Long non-coding RNA, UBE2CP3, HCC, Angiogenesis, ERK, VEGFA, Co-culture |
| title | Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma |
| title_full | Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma |
| title_fullStr | Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma |
| title_full_unstemmed | Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma |
| title_short | Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma |
| title_sort | long non coding rna ube2cp3 enhances hcc cell secretion of vegfa and promotes angiogenesis by activating erk1 2 hif 1α vegfa signalling in hepatocellular carcinoma |
| topic | Long non-coding RNA, UBE2CP3, HCC, Angiogenesis, ERK, VEGFA, Co-culture |
| url | http://link.springer.com/article/10.1186/s13046-018-0727-1 |
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