Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs

Ivan Vannini, Petra M. Wise, Kishore B Challagundla, Meropi Plousiou, Mirco Raffini, Erika Bandini, Francesca Fanini, Giorgia Paliaga, Melissa Crawford, Manuela Ferracin, Cristina Ivan, Linda Fabris, Ramana V. Davuluri, Zhiyi Guo, Maria Angelica Cortez, Xinna Zhang, Lu Chen, Shuxing Zhang, Cecilia Fernandez-Cymering, Leng Han & 14 others Silvia Carloni, Samanta Salvi, Hui Ling, Mariam Murtadha, Paolo Neviani, Barbara J. Gitlitz, Ite A. Laird-Offringa, Patrick Nana-Sinkam, Massimo Negrini, Han Liang, Dino Amadori, Amelia Cimmino, Muller Fabbri, George A. Calin

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1801
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

suppressors
MicroRNAs
Tumors
Carcinogenesis
tumors
cancer
Non-Small Cell Lung Carcinoma
lungs
Cells
Long Noncoding RNA
Neoplasms
Cyclins
Lung Neoplasms
decoys
Down-Regulation
Modulation
RNA
Cell Line
Survival
cultured cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs. / Vannini, Ivan; Wise, Petra M.; Challagundla, Kishore B; Plousiou, Meropi; Raffini, Mirco; Bandini, Erika; Fanini, Francesca; Paliaga, Giorgia; Crawford, Melissa; Ferracin, Manuela; Ivan, Cristina; Fabris, Linda; Davuluri, Ramana V.; Guo, Zhiyi; Cortez, Maria Angelica; Zhang, Xinna; Chen, Lu; Zhang, Shuxing; Fernandez-Cymering, Cecilia; Han, Leng; Carloni, Silvia; Salvi, Samanta; Ling, Hui; Murtadha, Mariam; Neviani, Paolo; Gitlitz, Barbara J.; Laird-Offringa, Ite A.; Nana-Sinkam, Patrick; Negrini, Massimo; Liang, Han; Amadori, Dino; Cimmino, Amelia; Fabbri, Muller; Calin, George A.

In: Nature communications, Vol. 8, No. 1, 1801, 01.12.2017.

Research output: Contribution to journalArticle

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, Fabbri, M & Calin, GA 2017, 'Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs', Nature communications, vol. 8, no. 1, 1801. https://doi.org/10.1038/s41467-017-01562-9
Vannini, Ivan ; Wise, Petra M. ; Challagundla, Kishore B ; Plousiou, Meropi ; Raffini, Mirco ; Bandini, Erika ; Fanini, Francesca ; Paliaga, Giorgia ; Crawford, Melissa ; Ferracin, Manuela ; Ivan, Cristina ; Fabris, Linda ; Davuluri, Ramana V. ; Guo, Zhiyi ; Cortez, Maria Angelica ; Zhang, Xinna ; Chen, Lu ; Zhang, Shuxing ; Fernandez-Cymering, Cecilia ; Han, Leng ; Carloni, Silvia ; Salvi, Samanta ; Ling, Hui ; Murtadha, Mariam ; Neviani, Paolo ; Gitlitz, Barbara J. ; Laird-Offringa, Ite A. ; Nana-Sinkam, Patrick ; Negrini, Massimo ; Liang, Han ; Amadori, Dino ; Cimmino, Amelia ; Fabbri, Muller ; Calin, George A. / Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs. In: Nature communications. 2017 ; Vol. 8, No. 1.
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AU - Wise, Petra M.

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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.

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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.

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