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.

Details

Title
Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs
Author
Vannini, Ivan 1 ; Wise, Petra M 2 ; Challagundla, Kishore B 3   VIAFID ORCID Logo  ; Plousiou, Meropi 1 ; Raffini, Mirco 1 ; Bandini, Erika 1 ; Fanini, Francesca 1 ; Paliaga, Giorgia 1 ; Crawford, Melissa 4 ; Ferracin, Manuela 5   VIAFID ORCID Logo  ; Ivan, Cristina 6   VIAFID ORCID Logo  ; Fabris, Linda 7 ; Davuluri, Ramana V 8 ; Guo, Zhiyi 9 ; Cortez, Maria Angelica 10   VIAFID ORCID Logo  ; Zhang, Xinna 11 ; Chen, Lu 12   VIAFID ORCID Logo  ; Zhang, Shuxing 12 ; Fernandez-Cymering, Cecilia 13 ; Leng, Han 14   VIAFID ORCID Logo  ; Carloni, Silvia 15 ; Salvi, Samanta 15 ; Ling, Hui 9 ; Murtadha, Mariam 2 ; Neviani, Paolo 2 ; Gitlitz, Barbara J 16 ; Laird-Offringa, Ite A 17 ; Nana-Sinkam, Patrick 18 ; Negrini, Massimo 19 ; Han, Liang 20   VIAFID ORCID Logo  ; Amadori, Dino 21 ; Cimmino, Amelia 22 ; Calin, George A 6 ; Muller Fabbri 2 

 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l., IRCCS, Gene Therapy Unit, Meldola (FC), Italy 
 Departments of Pediatrics and Molecular Microbiology & Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Children’s Center for Cancer and Blood Diseases and The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA, USA 
 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA 
 Department of Internal Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, USA 
 Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna, Bologna, Italy 
 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
 The Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
 Departments of Preventive Medicine and Neurological Surgery, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA 
 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
10  Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
11  The Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
12  Integrated Molecular Discovery Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
13  Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA 
14  Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA 
15  Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l., IRCCS, Biosciences Laboratory Unit, Meldola (FC), Italy 
16  Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA 
17  Departments of Surgery and Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA 
18  Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, USA 
19  Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy 
20  Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
21  Department of Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l., IRCCS, Meldola (FC), Italy 
22  Institute of Genetics and Biophysics, National Research Council, Naples, Italy 
Pages
1-19
Publication year
2017
Publication date
Nov 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1968994003
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.