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; 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

doi:10.1038/s41467-017-01562-9

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 HanSilvia 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

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 language	English (US)
Article number	1801
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-01562-9
State	Published - Dec 1 2017

ASJC Scopus subject areas

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-017-01562-9

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Vannini, I., Wise, P. M., Challagundla, K. B., Plousiou, M., Raffini, M., Bandini, E., Fanini, F., Paliaga, G., Crawford, M., Ferracin, M., Ivan, C., Fabris, L., Davuluri, R. V., Guo, Z., Cortez, M. A., Zhang, X., Chen, L., Zhang, S., Fernandez-Cymering, C., ... Calin, G. A. (2017). Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs. Nature communications, 8(1), Article 1801. https://doi.org/10.1038/s41467-017-01562-9

@article{f61672bb598c4146a409b8584cf66bcb,

title = "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.",

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

note = "Funding Information: Dr Fabbri is a St. Baldrick Foundation{\textquoteright}s Scholar and is supported by the NIH/NCI grant R01CA215753, Hyundai “Hope on Wheels”, the Pablove Foundation, STOP Cancer, the Jean Perkins Foundation, the Nautica Malibu Triathlon Funds, the award number P30CA014089 from the National Cancer Institute, the Hugh and Audy Lou Colvin Foundation Dr Calin is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. Work in Dr Calin{\textquoteright}s laboratory is supported by National Institutes of Health (NIH/ NCATS) Grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination (OSC), the NIH/NCI Grant 1 R01 CA182905-01, a U54 Grant—UPR/ MDACC Partnership for Excellence in Cancer Research 2016 Pilot Project, a Team DOD (CA160445P1) grant, a Ladies Leukemia League grant, a CLL Moonshot Flagship project, a SINF 2017 grant, and the Estate of C.G. Johnson, Jr A.C. was supported by the Italian Association for Cancer Research (AIRC-MFAG number 11510). Dr Laird-Offringa is supported by NIH Grant R01 HL114094 and the Labrecque Foundation. Shuxing Zhang is partially supported by NSF CHE-1411859. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-01562-9",

language = "English (US)",

volume = "8",

journal = "Nature communications",

issn = "2041-1723",

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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

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 - Funding Information: Dr Fabbri is a St. Baldrick Foundation’s Scholar and is supported by the NIH/NCI grant R01CA215753, Hyundai “Hope on Wheels”, the Pablove Foundation, STOP Cancer, the Jean Perkins Foundation, the Nautica Malibu Triathlon Funds, the award number P30CA014089 from the National Cancer Institute, the Hugh and Audy Lou Colvin Foundation Dr Calin is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. Work in Dr Calin’s laboratory is supported by National Institutes of Health (NIH/ NCATS) Grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination (OSC), the NIH/NCI Grant 1 R01 CA182905-01, a U54 Grant—UPR/ MDACC Partnership for Excellence in Cancer Research 2016 Pilot Project, a Team DOD (CA160445P1) grant, a Ladies Leukemia League grant, a CLL Moonshot Flagship project, a SINF 2017 grant, and the Estate of C.G. Johnson, Jr A.C. was supported by the Italian Association for Cancer Research (AIRC-MFAG number 11510). Dr Laird-Offringa is supported by NIH Grant R01 HL114094 and the Labrecque Foundation. Shuxing Zhang is partially supported by NSF CHE-1411859. 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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UR - http://www.scopus.com/inward/citedby.url?scp=85035772551&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-01562-9

DO - 10.1038/s41467-017-01562-9

M3 - Article

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AN - SCOPUS:85035772551

SN - 2041-1723

VL - 8

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 1801

ER -

Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs

Abstract

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