TY - JOUR
T1 - Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs
AU - Vannini, Ivan
AU - Wise, Petra M.
AU - Challagundla, Kishore B.
AU - Plousiou, Meropi
AU - Raffini, Mirco
AU - Bandini, Erika
AU - Fanini, Francesca
AU - Paliaga, Giorgia
AU - Crawford, Melissa
AU - Ferracin, Manuela
AU - Ivan, Cristina
AU - Fabris, Linda
AU - Davuluri, Ramana V.
AU - Guo, Zhiyi
AU - Cortez, Maria Angelica
AU - Zhang, Xinna
AU - Chen, Lu
AU - Zhang, Shuxing
AU - Fernandez-Cymering, Cecilia
AU - Han, Leng
AU - Carloni, Silvia
AU - Salvi, Samanta
AU - Ling, Hui
AU - Murtadha, Mariam
AU - Neviani, Paolo
AU - Gitlitz, Barbara J.
AU - Laird-Offringa, Ite A.
AU - Nana-Sinkam, Patrick
AU - Negrini, Massimo
AU - Liang, Han
AU - Amadori, Dino
AU - Cimmino, Amelia
AU - Fabbri, Muller
AU - Calin, George A.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-01562-9
DO - 10.1038/s41467-017-01562-9
M3 - Article
C2 - 29180617
AN - SCOPUS:85035772551
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1801
ER -