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Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs

Nat Commun. 2016; 
Vannini I, Wise PM, Challagundla KB, Plousiou M, Raffini M, Bandini E, Fanini F, Paliaga G, Crawford M, Ferracin M, Ivan C, Fabris L, Davuluri RV, Guo Z, Cortez MA, Zhang X, Chen L, Zhang S, Fernandez-Cymering C, Han L, Carloni S, Salvi S, Ling H, Murtadha M, Neviani P, Gitlitz BJ, Laird-Offringa IA, Nana-Sinkam P, Negrini M, Liang H, Amadori D, Cimmino A, Calin GA, Fabbri M.
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Gene Synthesis One pair of gRNAs were designed by GenScript flanking 24 bp of the core sequence “CCGGCTCCCGGGCCCCGCGGCGCC”.... gRNAs were cloned in the pSpCas9(BB)-2A-GFP(PX458) plasmid (GenScript), and wild-type H1299 cells were transfected with Lipofectamine 2000 (Invitrogen). Get A Quote

摘要

The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modu... More

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