A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi (n = 10) and primary malignant melanomas (n = 10), using quantitative real-...A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi (n = 10) and primary malignant melanomas (n = 10), using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase (Cdk) 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3'-untranslated regions (3'UTRs) of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.展开更多
The Berezovsk coal mine in western Siberia has yielded the most diverse Middle Jurassic limnic and terrestrial vertebrate assemblage of Asia. The vertebrate remains were recovered by screen washing from floodplain dep...The Berezovsk coal mine in western Siberia has yielded the most diverse Middle Jurassic limnic and terrestrial vertebrate assemblage of Asia. The vertebrate remains were recovered by screen washing from floodplain deposits on top of a thick coal seam of the Bathonian Itat Formation. A total of 29 vertebrate taxa has been recorded so far,including hybodontiform sharks,acipenseriforms,palaeonisciforms,amiiforms,dipnoans,anurans,caudates,turtles,squamates,choristoderans,crocodyliforms,pterosaurs,dinosaurs,tritylodontids,and a diverse mammaliaform and mammalian assemblage( eleutherodontids,docodontans,? amphilestids,dryolestids,and zatherians). The caudates are among the oldest in the fossil record and the anurans represent the oldest Asian record of this group. Among the mammals,Anthracolestes is the oldest and most basal known member of Dryolestidae and so far the only record from Asia. The vertebrate assemblage from the Berezovsk coal mine is very similar to that from the British Forest Marble Formation( Bathonian) and suggests a limited provincialism in the Middle Jurassic Laurasian landmass.展开更多
文摘A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi (n = 10) and primary malignant melanomas (n = 10), using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase (Cdk) 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3'-untranslated regions (3'UTRs) of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.
基金Financial support was provided by the Deutsche Forschungsgemeinschaft (DFG) (grant MA 1643 /14-1. 2)the Board of the President of the Russian Federation ( MD-802 . 2009 . 4 )+1 种基金the Russian Foundation for Basic Research ( projects 07 -04 -00393 ,10 -04 -01350 ,13 -04 -01401 ,and 11 -04 -91331 -NNIO)the Program of the Presidium of the Russian Academy of Sciences “Origin of the Life and Establishment of Biosphere
文摘The Berezovsk coal mine in western Siberia has yielded the most diverse Middle Jurassic limnic and terrestrial vertebrate assemblage of Asia. The vertebrate remains were recovered by screen washing from floodplain deposits on top of a thick coal seam of the Bathonian Itat Formation. A total of 29 vertebrate taxa has been recorded so far,including hybodontiform sharks,acipenseriforms,palaeonisciforms,amiiforms,dipnoans,anurans,caudates,turtles,squamates,choristoderans,crocodyliforms,pterosaurs,dinosaurs,tritylodontids,and a diverse mammaliaform and mammalian assemblage( eleutherodontids,docodontans,? amphilestids,dryolestids,and zatherians). The caudates are among the oldest in the fossil record and the anurans represent the oldest Asian record of this group. Among the mammals,Anthracolestes is the oldest and most basal known member of Dryolestidae and so far the only record from Asia. The vertebrate assemblage from the Berezovsk coal mine is very similar to that from the British Forest Marble Formation( Bathonian) and suggests a limited provincialism in the Middle Jurassic Laurasian landmass.