Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C
Abstract Angiogenesis is a significant character of lung adenocarcinoma (LUAD) and is an important reason leading to high mortality rates of LUAD patients. However, the molecular mechanisms of lncRNAs regulating the angiogenesis in LUAD have not been fully elucidated. Here we show lncRNA chromatin-a...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07452-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544348357885952 |
|---|---|
| author | Xiaolu Ge Chao Du Li Fang Wei Xu Juanjuan Xiang Jiheng Liu Ming Zhou Yuejun Chen Ziyao Wang Zheng Li |
| author_facet | Xiaolu Ge Chao Du Li Fang Wei Xu Juanjuan Xiang Jiheng Liu Ming Zhou Yuejun Chen Ziyao Wang Zheng Li |
| author_sort | Xiaolu Ge |
| collection | DOAJ |
| description | Abstract Angiogenesis is a significant character of lung adenocarcinoma (LUAD) and is an important reason leading to high mortality rates of LUAD patients. However, the molecular mechanisms of lncRNAs regulating the angiogenesis in LUAD have not been fully elucidated. Here we show lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis. Mechanistically, CAR10 could bind to Lactate Dehydrogenase A (LDHA) protein to regulate the phosphorylation and acetylation of LDHA and increase the dimerization of LDHA to promote its nuclear translocation, which increased the H3K79 methylation in Vascular Endothelial Growth Factor A (VEGFA) and Vascular Endothelial Growth Factor C (VEGFC) gene interval. CAR10 induced microvascular formation in vivo and in vitro by regulating LDHA-VEGFA/C axis. In addition, MYC and TP53 bonded to the promotor of CAR10 and reverse regulated its expression in LUAD cells. CAR10 regulates post-translational modification of LDHA and increases the H3K79 methylation of VEGFA/VEGFC to promote angiogenesis of LUAD, which is a potential therapeutic target for LUAD. |
| format | Article |
| id | doaj-art-3f52e2edcdd4482d8bf226c405e79493 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-3f52e2edcdd4482d8bf226c405e794932025-01-12T12:35:46ZengNature PortfolioCommunications Biology2399-36422025-01-018111410.1038/s42003-025-07452-xLong non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/CXiaolu Ge0Chao Du1Li Fang2Wei Xu3Juanjuan Xiang4Jiheng Liu5Ming Zhou6Yuejun Chen7Ziyao Wang8Zheng Li9Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong UniversityThe First Department of Thoracic Surgery, Hunan Cancer Hospital and the affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityNHC Key Laboratory of Carcinogenesis, Xiangya School of Basic Medical Sciences, Central South UniversityThe First Department of Thoracic Surgery, Hunan Cancer Hospital and the affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityThe First Department of Thoracic Surgery, Hunan Cancer Hospital and the affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityDepartment of Hematology & Oncology, First Hospital of ChangshaThe First Department of Thoracic Surgery, Hunan Cancer Hospital and the affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityNHC Key Laboratory of Carcinogenesis, Xiangya School of Basic Medical Sciences, Central South UniversityThe First Department of Thoracic Surgery, Hunan Cancer Hospital and the affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityThe First Department of Thoracic Surgery, Hunan Cancer Hospital and the affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityAbstract Angiogenesis is a significant character of lung adenocarcinoma (LUAD) and is an important reason leading to high mortality rates of LUAD patients. However, the molecular mechanisms of lncRNAs regulating the angiogenesis in LUAD have not been fully elucidated. Here we show lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis. Mechanistically, CAR10 could bind to Lactate Dehydrogenase A (LDHA) protein to regulate the phosphorylation and acetylation of LDHA and increase the dimerization of LDHA to promote its nuclear translocation, which increased the H3K79 methylation in Vascular Endothelial Growth Factor A (VEGFA) and Vascular Endothelial Growth Factor C (VEGFC) gene interval. CAR10 induced microvascular formation in vivo and in vitro by regulating LDHA-VEGFA/C axis. In addition, MYC and TP53 bonded to the promotor of CAR10 and reverse regulated its expression in LUAD cells. CAR10 regulates post-translational modification of LDHA and increases the H3K79 methylation of VEGFA/VEGFC to promote angiogenesis of LUAD, which is a potential therapeutic target for LUAD.https://doi.org/10.1038/s42003-025-07452-x |
| spellingShingle | Xiaolu Ge Chao Du Li Fang Wei Xu Juanjuan Xiang Jiheng Liu Ming Zhou Yuejun Chen Ziyao Wang Zheng Li Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C Communications Biology |
| title | Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C |
| title_full | Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C |
| title_fullStr | Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C |
| title_full_unstemmed | Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C |
| title_short | Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C |
| title_sort | long non coding rna car10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear ldha to epigenetically regulate vegfa c |
| url | https://doi.org/10.1038/s42003-025-07452-x |
| work_keys_str_mv | AT xiaoluge longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT chaodu longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT lifang longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT weixu longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT juanjuanxiang longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT jihengliu longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT mingzhou longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT yuejunchen longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT ziyaowang longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac AT zhengli longnoncodingrnacar10promotesangiogenesisoflungadenocarcinomabymediatingnuclearldhatoepigeneticallyregulatevegfac |