OBJECTIVE MicroR NA(miR NA)holds promise as a novel therapeutic tool for cancer treatment.However,the transfection efficiency of current delivery systems represents a bottleneck for clinical applications.Here,we demon...OBJECTIVE MicroR NA(miR NA)holds promise as a novel therapeutic tool for cancer treatment.However,the transfection efficiency of current delivery systems represents a bottleneck for clinical applications.Here,we demonstrate that gap junctions mediate an augmentative effect on the antiproliferation mediated by mi R-124-3p in U87 and C6 glioblastoma cells.METHODS The functional inhibition of gap junctions using either si RNA or pharmacological inhibition eliminated the mi R-124-3p-mediated antiproliferation,whereas the enhancement of gap junctions with retinoic acid treatment augmented this mi R-124-3p-mediated antiproliferation.A similar effect was observed in glioblastoma xenograft models.RESULTS More importantly,patch clamp and co-culture assays demonstrated the transmission of mi R-124-3p through gap junction channels into adjacent cells.In further exploring the impact of gap junction-mediated transport of mi R-124-3p on mi R-124-3p target pathways,we found that mi R-124-3p inhibited glioblastoma cell growth in part by decreasing the protein expression of cyclindependent kinase 6,leading to cel cycle arrest at the G0/G1phase;moreover,pharmacological regulation of gap junctions affected this cell cycle arrest.CONCLUSION Our results indicate that the″bystander″effects of functional gap junctions composed of connexin 43 enhance the antitumor effect of mi R-124-3p in glioblastoma cells by transferring mi R-124-3p to adjacent cells,thereby enhancing G0/G1cell cycle arrest.These observations provide a new guiding strategy for the clinical application of mi RNA therapy in tumor treatment.展开更多
We attempted to determine the first three-dimensional P and S wave velocity and Poisson's ratio structures of the lunar crust and mantle down to 1000 km depth under the near-side of the Moon by applying seismic to...We attempted to determine the first three-dimensional P and S wave velocity and Poisson's ratio structures of the lunar crust and mantle down to 1000 km depth under the near-side of the Moon by applying seismic tomography to the moonquake arrival-time data recorded by the Apollo seismic network operated during 1969 to 1977.Our results show that significant lateral heterogeneities may exist in the lunar interior.Because there is no plate tectonics in the Moon,the lateral heterogeneities may be produced at the early stage of the Moon formation and evolution,and they have been preserved till today.There seems to be a correlation between the distribution of deep moonquakes and lateral velocity variations in the lunar lower mantle,suggesting that the occurrence of deep moonquakes may be affected by the lunar structural heterogeneity in addition to the tidal stresses.Although this is an experimental work and the result is still preliminary,it indicates that tomographic imaging of the lunar interior is feasible.展开更多
基金The project supported by National Natural Science Foundation of China(81473234,U1303221)
文摘OBJECTIVE MicroR NA(miR NA)holds promise as a novel therapeutic tool for cancer treatment.However,the transfection efficiency of current delivery systems represents a bottleneck for clinical applications.Here,we demonstrate that gap junctions mediate an augmentative effect on the antiproliferation mediated by mi R-124-3p in U87 and C6 glioblastoma cells.METHODS The functional inhibition of gap junctions using either si RNA or pharmacological inhibition eliminated the mi R-124-3p-mediated antiproliferation,whereas the enhancement of gap junctions with retinoic acid treatment augmented this mi R-124-3p-mediated antiproliferation.A similar effect was observed in glioblastoma xenograft models.RESULTS More importantly,patch clamp and co-culture assays demonstrated the transmission of mi R-124-3p through gap junction channels into adjacent cells.In further exploring the impact of gap junction-mediated transport of mi R-124-3p on mi R-124-3p target pathways,we found that mi R-124-3p inhibited glioblastoma cell growth in part by decreasing the protein expression of cyclindependent kinase 6,leading to cel cycle arrest at the G0/G1phase;moreover,pharmacological regulation of gap junctions affected this cell cycle arrest.CONCLUSION Our results indicate that the″bystander″effects of functional gap junctions composed of connexin 43 enhance the antitumor effect of mi R-124-3p in glioblastoma cells by transferring mi R-124-3p to adjacent cells,thereby enhancing G0/G1cell cycle arrest.These observations provide a new guiding strategy for the clinical application of mi RNA therapy in tumor treatment.
基金Supported by Japan Society for the Promotion of Science (JSPS) to D. Zhao (Grant Nos.B-11440134 and A-17204037)
文摘We attempted to determine the first three-dimensional P and S wave velocity and Poisson's ratio structures of the lunar crust and mantle down to 1000 km depth under the near-side of the Moon by applying seismic tomography to the moonquake arrival-time data recorded by the Apollo seismic network operated during 1969 to 1977.Our results show that significant lateral heterogeneities may exist in the lunar interior.Because there is no plate tectonics in the Moon,the lateral heterogeneities may be produced at the early stage of the Moon formation and evolution,and they have been preserved till today.There seems to be a correlation between the distribution of deep moonquakes and lateral velocity variations in the lunar lower mantle,suggesting that the occurrence of deep moonquakes may be affected by the lunar structural heterogeneity in addition to the tidal stresses.Although this is an experimental work and the result is still preliminary,it indicates that tomographic imaging of the lunar interior is feasible.
