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Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs.


ABSTRACT: 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 modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call "entrapping". Our results support a key role for uc.339 in lung cancer.

SUBMITTER: Vannini I 

PROVIDER: S-EPMC5703849 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs.

Vannini Ivan I   Wise Petra M PM   Challagundla Kishore B KB   Plousiou Meropi M   Raffini Mirco M   Bandini Erika E   Fanini Francesca F   Paliaga Giorgia G   Crawford Melissa M   Ferracin Manuela M   Ivan Cristina C   Fabris Linda L   Davuluri Ramana V RV   Guo Zhiyi Z   Cortez Maria Angelica MA   Zhang Xinna X   Chen Lu L   Zhang Shuxing S   Fernandez-Cymering Cecilia C   Han Leng L   Carloni Silvia S   Salvi Samanta S   Ling Hui H   Murtadha Mariam M   Neviani Paolo P   Gitlitz Barbara J BJ   Laird-Offringa Ite A IA   Nana-Sinkam Patrick P   Negrini Massimo M   Liang Han H   Amadori Dino D   Cimmino Amelia A   Calin George A GA   Calin George A GA   Fabbri Muller M  

Nature communications 20171127 1


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 NSCL  ...[more]

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