Authors

Isidore Rigoutsos, Thomas Jefferson UniversityFollow
Sang Kil Lee, The University of Texas MD Anderson Cancer Center
Su Youn Nam, The University of Texas MD Anderson Cancer Center
Simone Anfossi, The University of Texas MD Anderson Cancer Center
Barbara Pasculli, The University of Texas MD Anderson Cancer Center
Martin Pichler, The University of Texas MD Anderson Cancer Center
Yi Jing, Thomas Jefferson UniversityFollow
Cristian Rodriguez-Aguayo, The University of Texas MD Anderson Cancer Center
Aristeidis G. Telonis, Thomas Jefferson UniversityFollow
Simona Rossi, The University of Texas MD Anderson Cancer Center
Cristina Ivan, The University of Texas MD Anderson Cancer Center
Tina Catela Ivkovic, The University of Texas MD Anderson Cancer Center
Linda Fabris, The University of Texas MD Anderson Cancer Center
Peter M. Clark, The Children's Hospital of Philadelphia
Hui Ling, The University of Texas MD Anderson Cancer Center
Masayoshi Shimizu, The University of Texas MD Anderson Cancer Center
Roxana S. Redis, The University of Texas MD Anderson Cancer Center
Maitri Y Shah, The University of Texas MD Anderson Cancer Center
Xinna Zhang, The University of Texas MD Anderson Cancer Center
Yoshinaga Okugawa, Baylor University Medical Center
Eun Jung Jung, Gyeongsang National University
Aristotelis Tsirigos, NYU Langone Medical Center
Li Huang, The University of Texas MD Anderson Cancer Center
Jana Ferdin, The University of Texas MD Anderson Cancer Center
Roberta Gafà, University of Ferrara
Riccardo Spizzo, The University of Texas MD Anderson Cancer Center
Milena S. Nicoloso, The University of Texas MD Anderson Cancer Center
Anurag N. Paranjape, The University of Texas MD Anderson Cancer Center
Maryam Shariati, The University of Texas MD Anderson Cancer Center
Aida Tiron, Nassau University Medical Center
Jen Jen Yeh, University of North Carolina at Chapel Hill
Raul Teruel-Montoya, The University of Texas MD Anderson Cancer Center
Lianchun Xiao, The University of Texas MD Anderson Cancer Center
Sonia A. Melo, Porto University
David Menter, The University of Texas MD Anderson Cancer Center
Zhi-Qin Jiang, The University of Texas MD Anderson Cancer Center
Elsa R. Flores, Moffitt Cancer Center
Massimo Negrini, University of Ferrara
Ajay Goel, Baylor University Medical Center
Menashe Bar-Eli, The University of Texas MD Anderson Cancer Center
Sendurai A. Mani, The University of Texas MD Anderson Cancer Center
Chang Gong Liu, The University of Texas MD Anderson Cancer Center
Gabriel Lopez-Berestein, The University of Texas MD Anderson Cancer Center
Ioana Berindan-Neagoe, The University of Texas MD Anderson Cancer Center
Manel Esteller, University of Barcelona
Scott Kopetz, The University of Texas MD Anderson Cancer Center
Giovanni Lanza, University of Ferrara
George A. Calin, The University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

5-24-2017

Comments

This article has been peer reviewed. It is the author’s final published version in Genome Biology

Volume 8, Issue 1, May 2017, Article number 98.

The published version is available at DOI: 10.1186/s13059-017-1224-0. Copyright © Rigoutsos et al.

Abstract

BACKGROUND: Non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion.

RESULTS: We performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients' overall survival.

CONCLUSIONS: The primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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