Exosomes encompass a great deal of valuable biological information and play a crit-ical role in tumor development.However,the mechanism of exosomal lncRNAs remains poorly elucidated in bladder cancer(BCa).In this stud...Exosomes encompass a great deal of valuable biological information and play a crit-ical role in tumor development.However,the mechanism of exosomal lncRNAs remains poorly elucidated in bladder cancer(BCa).In this study,we identified exosomal lnc-TAF12e2:1 as a novel biomarker in BCa diagnosis and aimed to investigate the underlying biological function.Dual luciferase reporter assay,RNA immunoprecipitation(RIP),RNA pulldown assays,and xenograft mouse model were used to verify the competitive endogenous RNA mechanism of lnc-TAF12e2:1.We found exosomal lnc-TAF12e2:1 up-regulated in urinary exosomes,tumor tissues of patients,and BCa cells.Down-regulation of lnc-TAF12e2:1 impaired BCa cell prolif-eration and migration,and promoted cell cycle arrest at the G0/G1 phase and cell apoptosis.The opposite effects were also observed when lnc-TAF12e2:1 was overexpressed.lnc-TAF12 e2:1 was transferred by intercellular exosomes to modulate malignant biological behavior.Mechanistically,lnc-TAF12e2:1 packaged in the exosomes relieved the miRNA-mediated silence effect on ASB12 via serving as a sponger of miR-7847e3p to accelerate progression in BCa.ASB12 was also first proved as an oncogene to promote cell proliferation and migration and depress cell cycle arrest and cell apoptosis in our data.In conclusion,exosomal lnc-TAF12e2:1,located in the cytoplasm of BCa,might act as a competitive endogenous RNA to competitively bind to miR-7847e3p,and then be involved in miR-7847e3p/ASB12 regulatory axis to promote tumorigenesis,which provided a deeper insight into the molecular mechanism of BCa.展开更多
基金funded by Wuhan University(No.4206e413100049)the Science and Technology Department of Hubei Province Key Project(China)(No.2022EJD001)+3 种基金Zhongnan Hospital of Wuhan University(No.ZNYQ2023002,KY0100000109)the Fundamental Research Funds for the Central Universities(China)(No.2042022dx0003)Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2020-PT320-004)Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(No.2022QNRC001).
文摘Exosomes encompass a great deal of valuable biological information and play a crit-ical role in tumor development.However,the mechanism of exosomal lncRNAs remains poorly elucidated in bladder cancer(BCa).In this study,we identified exosomal lnc-TAF12e2:1 as a novel biomarker in BCa diagnosis and aimed to investigate the underlying biological function.Dual luciferase reporter assay,RNA immunoprecipitation(RIP),RNA pulldown assays,and xenograft mouse model were used to verify the competitive endogenous RNA mechanism of lnc-TAF12e2:1.We found exosomal lnc-TAF12e2:1 up-regulated in urinary exosomes,tumor tissues of patients,and BCa cells.Down-regulation of lnc-TAF12e2:1 impaired BCa cell prolif-eration and migration,and promoted cell cycle arrest at the G0/G1 phase and cell apoptosis.The opposite effects were also observed when lnc-TAF12e2:1 was overexpressed.lnc-TAF12 e2:1 was transferred by intercellular exosomes to modulate malignant biological behavior.Mechanistically,lnc-TAF12e2:1 packaged in the exosomes relieved the miRNA-mediated silence effect on ASB12 via serving as a sponger of miR-7847e3p to accelerate progression in BCa.ASB12 was also first proved as an oncogene to promote cell proliferation and migration and depress cell cycle arrest and cell apoptosis in our data.In conclusion,exosomal lnc-TAF12e2:1,located in the cytoplasm of BCa,might act as a competitive endogenous RNA to competitively bind to miR-7847e3p,and then be involved in miR-7847e3p/ASB12 regulatory axis to promote tumorigenesis,which provided a deeper insight into the molecular mechanism of BCa.
