LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma
High levels of microvessel density (MVD) indicate poor prognosis in patients with malignant glioma. Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3, a potential tumor suppressor, plays an important role in tumor progression and may serve as a biomarker in many human cancers. However, i...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.621154/full |
| _version_ | 1818850002535972864 |
|---|---|
| author | Chenghao Peng Chenghao Peng Hanmin Chen Youwei Li Hang Yang Peizhong Qin Baojun Ma Qiuhong Duan Baofeng Wang Feng Mao Dongsheng Guo |
| author_facet | Chenghao Peng Chenghao Peng Hanmin Chen Youwei Li Hang Yang Peizhong Qin Baojun Ma Qiuhong Duan Baofeng Wang Feng Mao Dongsheng Guo |
| author_sort | Chenghao Peng |
| collection | DOAJ |
| description | High levels of microvessel density (MVD) indicate poor prognosis in patients with malignant glioma. Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3, a potential tumor suppressor, plays an important role in tumor progression and may serve as a biomarker in many human cancers. However, its role and underlying mechanism of action in glioma angiogenesis remain unclear. In the present study, we used loss- and gain-of-function assays to show that LRIG3 significantly suppressed glioma-induced angiogenesis, both in vitro and in vivo. Mechanistically, LRIG3 inhibited activation of the PI3K/AKT signaling pathway, downregulating vascular endothelial growth factor A (VEGFA) in glioma cells, thereby inhibiting angiogenesis. Notably, LRIG3 had a significant negative correlation with VEGFA expression in glioma tissues. Taken together, our results suggest that LRIG3 is a novel regulator of glioma angiogenesis and may be a promising option for developing anti-angiogenic therapy. |
| first_indexed | 2024-12-19T06:42:12Z |
| format | Article |
| id | doaj.art-4818541c7f394f8eb1e707fc78ceb17f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T06:42:12Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4818541c7f394f8eb1e707fc78ceb17f2022-12-21T20:32:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011110.3389/fonc.2021.621154621154LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in GliomaChenghao Peng0Chenghao Peng1Hanmin Chen2Youwei Li3Hang Yang4Peizhong Qin5Baojun Ma6Qiuhong Duan7Baofeng Wang8Feng Mao9Dongsheng Guo10Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHigh levels of microvessel density (MVD) indicate poor prognosis in patients with malignant glioma. Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3, a potential tumor suppressor, plays an important role in tumor progression and may serve as a biomarker in many human cancers. However, its role and underlying mechanism of action in glioma angiogenesis remain unclear. In the present study, we used loss- and gain-of-function assays to show that LRIG3 significantly suppressed glioma-induced angiogenesis, both in vitro and in vivo. Mechanistically, LRIG3 inhibited activation of the PI3K/AKT signaling pathway, downregulating vascular endothelial growth factor A (VEGFA) in glioma cells, thereby inhibiting angiogenesis. Notably, LRIG3 had a significant negative correlation with VEGFA expression in glioma tissues. Taken together, our results suggest that LRIG3 is a novel regulator of glioma angiogenesis and may be a promising option for developing anti-angiogenic therapy.https://www.frontiersin.org/articles/10.3389/fonc.2021.621154/fullgliomaangiogenesisLRIG3vascular endothelial growth factor API3K/AKT |
| spellingShingle | Chenghao Peng Chenghao Peng Hanmin Chen Youwei Li Hang Yang Peizhong Qin Baojun Ma Qiuhong Duan Baofeng Wang Feng Mao Dongsheng Guo LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma Frontiers in Oncology glioma angiogenesis LRIG3 vascular endothelial growth factor A PI3K/AKT |
| title | LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma |
| title_full | LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma |
| title_fullStr | LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma |
| title_full_unstemmed | LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma |
| title_short | LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma |
| title_sort | lrig3 suppresses angiogenesis by regulating the pi3k akt vegfa signaling pathway in glioma |
| topic | glioma angiogenesis LRIG3 vascular endothelial growth factor A PI3K/AKT |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.621154/full |
| work_keys_str_mv | AT chenghaopeng lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT chenghaopeng lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT hanminchen lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT youweili lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT hangyang lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT peizhongqin lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT baojunma lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT qiuhongduan lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT baofengwang lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT fengmao lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma AT dongshengguo lrig3suppressesangiogenesisbyregulatingthepi3kaktvegfasignalingpathwayinglioma |