Discovery of Novel Anti-tumour Agents for Specific Recognizing the G-quadruplex in 5'-Untranslated Region of Human Vascular Endothelial Growth Factor(hVEGF)
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- 英文论文题名：Discovery of Novel Anti-tumour Agents for Specific Recognizing the G-quadruplex in 5'-Untranslated Region of Human Vascular Endothelial Growth Factor(hVEGF)
- 论文作者：王世珂 ; Yue Wu ; Xiao-Qin Wang ; Guo-Tao Kuang ; Qi Zhang ; Giulia Biffi ; Shu-Ling Lin ; Hui-Yun Liu ; Jia-Heng Tan ; Zhi-Shu Huang ; Lian-Quan Gu ; Tian-Miao Ou
- 英文论文作者：Shi-Ke Wang ; Yue Wu ; Xiao-Qin Wang ; Guo-Tao Kuang ; Qi Zhang ; Giulia Biffi ; Shu-Ling Lin ; Hui-Yun Liu ; Jia-Heng Tan ; Zhi-Shu Huang ; Lian-Quan Gu ; Tian-Miao Ou ; School of Pharmaceutical Sciences ; Sun Yat-sen University ; School of Pharmacy ; Guangdong Medical College ; Cancer Research UK Cambridge Institute ; University of Cambridge ; Li Ka Shing Centre
- 年：2016
- 作者机构：中山大学药学院;School of Pharmacy,Guangdong Medical College;Cancer Research UK Cambridge Institute,University of Cambridge,Li Ka Shing Centre;
- 英文论文关键词：VEGF ; translational regulation ; G-quadruplex ; quinazoline derivative ; antitumor
- 会议召开时间：2016-09-25
- 会议录名称：第九届全国核糖核酸学术讨论会论文集
- 语种：英文
- 分类号：R979.1
- 学会代码：IGSS
- 会议名称：第九届全国核糖核酸学术讨论会
- 会议地点：中国上海
- 主办单位：中国生物化学与分子生物学会核糖核酸专业委员会
- 学会名称：中国生物化学与分子生物学会
- 页数：1
- 文件大小：496k
- 原文格式：D
- 会议级别：全国
摘要
Angiogenesis is important in tumorigenesis and tumor progress.Human vascular endothelial growth factor(h VEGF)is an angiogenic growth factor that plays a crucial role in tumor progression.The G-rich region within the 5’-untranslated region(5’-UTR)of h VEGF m RNA can form a‘switchable’RNA G-quadruplex structure that is essential for a cap-independent translation initiation.We firstly screen our small-molecule library for binders of this G-tract.As a result,a novel quinazoline derivative compound 1shows a significant specific interaction with the G-tract and destabilizes the Gquadruplex structure.Cellular experiments results reveal that compound 1 downregulates h VEGF translation,and significantly impedes tumor cells migration.We also find thatcompound1exhibitsan obvious tumor inhibiting activity in MCF-7 xenograft tumors,which may relate with its ability to reduce h VEGF expression.These findings provide a new way of h VEGF translational control through interacting with Gquadruplex structure in the 5’UTRby small molecules.
Angiogenesis is important in tumorigenesis and tumor progress.Human vascular endothelial growth factor(h VEGF) is an angiogenic growth factor that plays a crucial role in tumor progression.The G-rich region within the 5'-untranslated region(5'-UTR) of h VEGF m RNA can form a ‘switchable' RNA G-quadruplex structure that is essential for a cap-independent translation initiation.We firstly screen our small-molecule library for binders of this G-tract.As a result,a novel quinazoline derivative compound 1 shows a significant specific interaction with the G-tract and destabilizes the Gquadruplex structure.Cellular experiments results reveal that compound 1 downregulates h VEGF translation,and significantly impedes tumor cells migration.We also find thatcompound1 exhibitsan obvious tumor inhibiting activity in MCF-7 xenograft tumors,which may relate with its ability to reduce h VEGF expression.These findings provide a new way of h VEGF translational control through interacting with Gquadruplex structure in the 5'UTRby small molecules.
Angiogenesis is important in tumorigenesis and tumor progress.Human vascular endothelial growth factor(h VEGF) is an angiogenic growth factor that plays a crucial role in tumor progression.The G-rich region within the 5'-untranslated region(5'-UTR) of h VEGF m RNA can form a ‘switchable' RNA G-quadruplex structure that is essential for a cap-independent translation initiation.We firstly screen our small-molecule library for binders of this G-tract.As a result,a novel quinazoline derivative compound 1 shows a significant specific interaction with the G-tract and destabilizes the Gquadruplex structure.Cellular experiments results reveal that compound 1 downregulates h VEGF translation,and significantly impedes tumor cells migration.We also find thatcompound1 exhibitsan obvious tumor inhibiting activity in MCF-7 xenograft tumors,which may relate with its ability to reduce h VEGF expression.These findings provide a new way of h VEGF translational control through interacting with Gquadruplex structure in the 5'UTRby small molecules.
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