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N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

By Calin GA Lanza G Kopetz S Esteller M Berindan-Neagoe I Lopez-Berestein G Liu CG Mani SA Bar-Eli M Goel A Negrini M Flores ER Jiang ZQ Menter D Melo SA Xiao L Teruel-Montoya R Yeh JJ Tiron A Shariati M Paranjape AN Nicoloso MS Spizzo R Gafà R Ferdin J Huang L Tsirigos A Jung EJ Okugawa Y1 Zhang X Shah MY Redis RS Shimizu M Ling H Clark PM Fabris L Catela Ivkovic T Ivan C Rossi S Telonis AG Rodriguez-Aguayo C Jing Y Pichler M Pasculli B Anfossi S Nam SY Lee SK Rigoutsos I

Abstract

Background: Non-coding RNAs have been drawing increasing attention in recent years as functional data suggest\ud that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that\ud modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer\ud invasion.\ud Results: We performed multivariate analyses of data from two independent cohorts of colorectal cancer patients\ud and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient\ud survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk\ud with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long\ud DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these\ud findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We\ud found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer\ud and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the\ud colorectal cancer patients’ overall survival.\ud Conclusions: The primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie\ud metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional\ud pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human\ud genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of\ud biomarkers and therapeutic targets that are primate-specifi

Topics: Non-coding RNA, Pyknons, Transcription, ncRNA, lncRNA, N-BLR, EMT, CRC,
Year: 2017
DOI identifier: 10.1186/s13059-017-1224-0
OAI identifier: oai:iris.unife.it:11392/2376356
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