LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis
BackgroundLong non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.MethodsRT-qPCR and fluorescence in situ hybridzation (FISH) were conducted to detect the expression of...
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Frontiers Media S.A.
2021-09-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.705697/full |
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author | Yangwei Xu Yangwei Xu Yanyan Li Yanyan Li Yue Qiu Yue Qiu Fei Sun Guifang Zhu Jingbo Sun Jingbo Sun Guixing Cai Wanmei Lin Wanmei Lin Yun Fu Yun Fu Hongmei Wu Hongmei Wu Shanshan Jiang Shanshan Jiang Zhihui Wen Zhihui Wen Feiyan Feng Feiyan Feng Junjie Luo Junjie Luo Yuqin Yang Yuqin Yang Qingling Zhang Qingling Zhang |
author_facet | Yangwei Xu Yangwei Xu Yanyan Li Yanyan Li Yue Qiu Yue Qiu Fei Sun Guifang Zhu Jingbo Sun Jingbo Sun Guixing Cai Wanmei Lin Wanmei Lin Yun Fu Yun Fu Hongmei Wu Hongmei Wu Shanshan Jiang Shanshan Jiang Zhihui Wen Zhihui Wen Feiyan Feng Feiyan Feng Junjie Luo Junjie Luo Yuqin Yang Yuqin Yang Qingling Zhang Qingling Zhang |
author_sort | Yangwei Xu |
collection | DOAJ |
description | BackgroundLong non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.MethodsRT-qPCR and fluorescence in situ hybridzation (FISH) were conducted to detect the expression of lncRNA NEAT1 in GC tissues and cell lines. Gene Set Enrichment Analysis (GSEA) was performed to screen out potential phenotypes and pathways that NEAT1 may participate in. NEAT1-silenced AGS and MGC803 cells were constructed and a series of functional experiments to investigate the roles of NEAT1 in GC angiogenesis both in vitro and in vivo. RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.ResultsWe observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. In vitro experiments showed that NEAT1 promoted GC angiogenesis by enhancing proliferation, migration, and tube formation ability of endothelial cells. Mechanism researches revealed that NEAT1 could competitively sponge miR-17-5p which targeted TGFβR2 directly. Subsequently, activate TGFβ/Smad pathway by following with upregulation of a series of classical proangiogenic factors especially VEGF.ConclusionThe study unveiled that the LncRNA NEAT1/miR-17-5p/TGFβR2 axis is a novel mechanism in GC angiogenesis. Disrupting this axis may be a potential strategy for GC treatment. |
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spelling | doaj.art-4ef5e455e61e4b1dba77e2e43204b6082022-12-21T23:16:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.705697705697LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated AngiogenesisYangwei Xu0Yangwei Xu1Yanyan Li2Yanyan Li3Yue Qiu4Yue Qiu5Fei Sun6Guifang Zhu7Jingbo Sun8Jingbo Sun9Guixing Cai10Wanmei Lin11Wanmei Lin12Yun Fu13Yun Fu14Hongmei Wu15Hongmei Wu16Shanshan Jiang17Shanshan Jiang18Zhihui Wen19Zhihui Wen20Feiyan Feng21Feiyan Feng22Junjie Luo23Junjie Luo24Yuqin Yang25Yuqin Yang26Qingling Zhang27Qingling Zhang28Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaNanfang Hospital, First Clinical Medical School, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaNanfang Hospital, First Clinical Medical School, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaNanfang Hospital, First Clinical Medical School, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaBackgroundLong non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.MethodsRT-qPCR and fluorescence in situ hybridzation (FISH) were conducted to detect the expression of lncRNA NEAT1 in GC tissues and cell lines. Gene Set Enrichment Analysis (GSEA) was performed to screen out potential phenotypes and pathways that NEAT1 may participate in. NEAT1-silenced AGS and MGC803 cells were constructed and a series of functional experiments to investigate the roles of NEAT1 in GC angiogenesis both in vitro and in vivo. RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.ResultsWe observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. In vitro experiments showed that NEAT1 promoted GC angiogenesis by enhancing proliferation, migration, and tube formation ability of endothelial cells. Mechanism researches revealed that NEAT1 could competitively sponge miR-17-5p which targeted TGFβR2 directly. Subsequently, activate TGFβ/Smad pathway by following with upregulation of a series of classical proangiogenic factors especially VEGF.ConclusionThe study unveiled that the LncRNA NEAT1/miR-17-5p/TGFβR2 axis is a novel mechanism in GC angiogenesis. Disrupting this axis may be a potential strategy for GC treatment.https://www.frontiersin.org/articles/10.3389/fcell.2021.705697/fullLncRNA NEAT1miR-17-5pgastric cancerTGFβR2angiogenesisprogression |
spellingShingle | Yangwei Xu Yangwei Xu Yanyan Li Yanyan Li Yue Qiu Yue Qiu Fei Sun Guifang Zhu Jingbo Sun Jingbo Sun Guixing Cai Wanmei Lin Wanmei Lin Yun Fu Yun Fu Hongmei Wu Hongmei Wu Shanshan Jiang Shanshan Jiang Zhihui Wen Zhihui Wen Feiyan Feng Feiyan Feng Junjie Luo Junjie Luo Yuqin Yang Yuqin Yang Qingling Zhang Qingling Zhang LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis Frontiers in Cell and Developmental Biology LncRNA NEAT1 miR-17-5p gastric cancer TGFβR2 angiogenesis progression |
title | LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis |
title_full | LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis |
title_fullStr | LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis |
title_full_unstemmed | LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis |
title_short | LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis |
title_sort | lncrna neat1 promotes gastric cancer progression through mir 17 5p tgfβr2 axis up regulated angiogenesis |
topic | LncRNA NEAT1 miR-17-5p gastric cancer TGFβR2 angiogenesis progression |
url | https://www.frontiersin.org/articles/10.3389/fcell.2021.705697/full |
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