Lingnan He1,2, Anqi Feng1, Hui Guo3, Haohao Huang4, Qingchun Deng5, Ende Zhao6, Ming Yang7. 1. Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai, China. 2. Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, Hubei, China. 3. Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, 430022, Hubei, China. 4. Department of Neurosurgery, General Hospital of Central Theater Command of Chinese People's Liberation Army, 627 Wuluo Road, Wuchang District, Wuhan, Hubei, China. 5. Department of Gynecology, The Second Affiliated Hospital of Hainan Medical University, No. 48, Baishitang Road, Longhua District, Haikou, 570102, Hainan, China. 6. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, 430022, Hubei, China. 7. Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, 430022, Hubei, China. mingyang74@hust.edu.cn.
Abstract
BACKGROUND: Increasing evidence indicates that leucine-rich-alpha-2-glycoprotein 1 (LRG1) is associated with multiple malignancies, but whether it participates in gastric cancer (GC) angiogenesis remains unclear. METHODS: The expression levels of LRG1 were assessed in GC samples. Endothelial tube formation analysis, HUVEC migration assay, chorioallantoic membrane assay (CAM), and xenograft tumor model were used to investigate the effect of LRG1 on angiogenesis in gastric cancer. The involvement of activating transcription factor 3 (ATF3) was analyzed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. Western blot and enzyme-linked immunosorbent assay were performed to measure the SRC/STAT3/VEGFA pathway. RESULTS: LRG1 was overexpressed in GC tissues and associated with cancer angiogenesis. In addition, LRG1 markedly promoted GC cell proliferation in vitro and in vivo. Moreover, overexpression of LRG1 could stimulate GC angiogenesis in vitro and in vivo. Then, we identified ATF3 promotes the transcription of LRG1 and is a positive regulator of angiogenesis. Additionally, LRG1 could activate VEGFA expression via the SRC/STAT3/ VEGFA pathway in GC cells, thus contributing to the angiogenesis of GC. CONCLUSIONS: The present study suggests LRG1 plays a crucial role in the regulation of angiogenesis in GC and could be a potential therapeutic target for GC.
BACKGROUND: Increasing evidence indicates that leucine-rich-alpha-2-glycoprotein 1 (LRG1) is associated with multiple malignancies, but whether it participates in gastric cancer (GC) angiogenesis remains unclear. METHODS: The expression levels of LRG1 were assessed in GC samples. Endothelial tube formation analysis, HUVEC migration assay, chorioallantoic membrane assay (CAM), and xenograft tumor model were used to investigate the effect of LRG1 on angiogenesis in gastric cancer. The involvement of activating transcription factor 3 (ATF3) was analyzed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. Western blot and enzyme-linked immunosorbent assay were performed to measure the SRC/STAT3/VEGFA pathway. RESULTS: LRG1 was overexpressed in GC tissues and associated with cancer angiogenesis. In addition, LRG1 markedly promoted GC cell proliferation in vitro and in vivo. Moreover, overexpression of LRG1 could stimulate GC angiogenesis in vitro and in vivo. Then, we identified ATF3 promotes the transcription of LRG1 and is a positive regulator of angiogenesis. Additionally, LRG1 could activate VEGFA expression via the SRC/STAT3/ VEGFA pathway in GC cells, thus contributing to the angiogenesis of GC. CONCLUSIONS: The present study suggests LRG1 plays a crucial role in the regulation of angiogenesis in GC and could be a potential therapeutic target for GC.