Dear Editor,In the modernization of traditional Chinese medicine(TCM),two key aspects are determining the active ingredients in herbs and elucidating the mechanism of action between the active ingredients and targets....Dear Editor,In the modernization of traditional Chinese medicine(TCM),two key aspects are determining the active ingredients in herbs and elucidating the mechanism of action between the active ingredients and targets.The construction of a comprehensive and highly-reliability TCM database is highly desirable.Since its establishment in 2011,our TCM Database@Taiwan1 has been used extensively and heavily cited,and it also has been included in the ZINC database.2 Using natural language processing,we set up a knowledge graph and molecular signaling pathways to establish a TCM database,TCMBank(https://TCMBank.cn/),which extends from TCM Database@Taiwan and includes 9192 herbs,61,966 ingredients,15,179 targets,and 32,529 diseases.The updated TCMBank expanded the number of herbal ingredients from 32,364 to 61,966(unduplicated),and two new data fields,targets,and diseases,have been added.The number of herbs with connection information is 9010,and the average number of connection edges of herbs is 16.05.The number of ingredients with connection information is 54,676,and the average number of connection edges of herbs is 5.26.展开更多
Background:Aquaporin 9(AQP9)is permeable to water or other small molecules,and plays an important role in various cancers.We previously found that AQP9 was related to the efficacy of chemotherapy in patients with colo...Background:Aquaporin 9(AQP9)is permeable to water or other small molecules,and plays an important role in various cancers.We previously found that AQP9 was related to the efficacy of chemotherapy in patients with colorectal cancer(CRC).This study aimed to identify the role and regulatory mechanism of AQP9 in CRC metastasis.Methods:The clinical significance of AQP9 was analysed by using bioinformatics and tissue microarray.Transcriptome sequencing,Dual-Luciferase Reporter Assay,Biacore,and co-immunoprecipitation were employed to demonstrate the regulatory mechanism of AQP9 in CRC.The relationship between AQP9 and CRC metastasis was verified in vitro and in vivo by using real-time cell analysis assay,high content screening,and liver metastasis models of nude mice.Results:We found that AQP9 was highly expressed in metastatic CRC.AQP9 overexpression reduced cell roundness and enhanced cell motility in CRC.We further showed that AQP9 interacted with Dishevelled 2(DVL2)via the C-terminal SVIM motif,resulting in DVL2 stabilization and the Wnt/b-catenin pathway activation.Additionally,we identified the E3 ligase neural precursor cell expressed developmentally downregulated 4-like(NEDD4L)as a modulator regulating the ubiquitination and degradation of AQP9.Conclusions:Collectively,our study revealed the important role of AQP9 in regulating DVL2 stabilization and Wnt/β-catenin signaling to promote CRC metastasis.Targeting the NEDD4L–AQP9–DVL2 axis might have therapeutic usefulness in metastatic CRC treatment.展开更多
基金the National Natural Science Foundation of China(Grant No.62176272).
文摘Dear Editor,In the modernization of traditional Chinese medicine(TCM),two key aspects are determining the active ingredients in herbs and elucidating the mechanism of action between the active ingredients and targets.The construction of a comprehensive and highly-reliability TCM database is highly desirable.Since its establishment in 2011,our TCM Database@Taiwan1 has been used extensively and heavily cited,and it also has been included in the ZINC database.2 Using natural language processing,we set up a knowledge graph and molecular signaling pathways to establish a TCM database,TCMBank(https://TCMBank.cn/),which extends from TCM Database@Taiwan and includes 9192 herbs,61,966 ingredients,15,179 targets,and 32,529 diseases.The updated TCMBank expanded the number of herbal ingredients from 32,364 to 61,966(unduplicated),and two new data fields,targets,and diseases,have been added.The number of herbs with connection information is 9010,and the average number of connection edges of herbs is 16.05.The number of ingredients with connection information is 54,676,and the average number of connection edges of herbs is 5.26.
基金supported by the National Natural Science Foundation of China[No.81702330 to Z.Y.]Guangdong Natural Science Foundation[No.2021A1515011400 to Z.Y.].
文摘Background:Aquaporin 9(AQP9)is permeable to water or other small molecules,and plays an important role in various cancers.We previously found that AQP9 was related to the efficacy of chemotherapy in patients with colorectal cancer(CRC).This study aimed to identify the role and regulatory mechanism of AQP9 in CRC metastasis.Methods:The clinical significance of AQP9 was analysed by using bioinformatics and tissue microarray.Transcriptome sequencing,Dual-Luciferase Reporter Assay,Biacore,and co-immunoprecipitation were employed to demonstrate the regulatory mechanism of AQP9 in CRC.The relationship between AQP9 and CRC metastasis was verified in vitro and in vivo by using real-time cell analysis assay,high content screening,and liver metastasis models of nude mice.Results:We found that AQP9 was highly expressed in metastatic CRC.AQP9 overexpression reduced cell roundness and enhanced cell motility in CRC.We further showed that AQP9 interacted with Dishevelled 2(DVL2)via the C-terminal SVIM motif,resulting in DVL2 stabilization and the Wnt/b-catenin pathway activation.Additionally,we identified the E3 ligase neural precursor cell expressed developmentally downregulated 4-like(NEDD4L)as a modulator regulating the ubiquitination and degradation of AQP9.Conclusions:Collectively,our study revealed the important role of AQP9 in regulating DVL2 stabilization and Wnt/β-catenin signaling to promote CRC metastasis.Targeting the NEDD4L–AQP9–DVL2 axis might have therapeutic usefulness in metastatic CRC treatment.
