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

Isidore Rigoutsos, Sang Kil Lee, Su Youn Nam, Simone Anfossi, Barbara Pasculli, Martin Pichler, Yi Jing, Cristian Rodriguez-Aguayo, Aristeidis G. Telonis, Simona Rossi, Cristina Ivan, Tina Catela Ivkovic, Linda Fabris, Peter M. Clark, Hui Ling, Masayoshi Shimizu, Roxana S. Redis, Maitri Y. Shah, Xinna Zhang, Yoshinaga OkugawaEun Jung Jung, Aristotelis Tsirigos, Li Huang, Jana Ferdin, Roberta Gafà, Riccardo Spizzo, Milena S. Nicoloso, Anurag N. Paranjape, Maryam Shariati, Aida Tiron, Jen Jen Yeh, Raul Teruel-Montoya, Lianchun Xiao, Sonia A. Melo, David Menter, Zhi Qin Jiang, Elsa R. Flores, Massimo Negrini, Ajay Goel, Menashe Bar-Eli, Sendurai A. Mani, Chang Gong Liu, Gabriel Lopez-Berestein, Ioana Berindan-Neagoe, Manel Esteller, Scott Kopetz, Giovanni Lanza, George A. Calin

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Article number98
JournalGenome biology
Volume18
Issue number1
DOIs
Publication statusPublished - 2017 May 24

Fingerprint

colorectal neoplasms
primate
Primates
Colorectal Neoplasms
cancer
loci
biomarker
RNA
biomarkers
genomics
Biomarkers
Long Noncoding RNA
Untranslated RNA
lymphocytic leukemia
Nucleotide Motifs
Epithelial-Mesenchymal Transition
Survival
cadherins
Human Genome
B-Cell Chronic Lymphocytic Leukemia

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Cite this

Rigoutsos, Isidore ; Lee, Sang Kil ; Nam, Su Youn ; Anfossi, Simone ; Pasculli, Barbara ; Pichler, Martin ; Jing, Yi ; Rodriguez-Aguayo, Cristian ; Telonis, Aristeidis G. ; Rossi, Simona ; Ivan, Cristina ; Catela Ivkovic, Tina ; Fabris, Linda ; Clark, Peter M. ; Ling, Hui ; Shimizu, Masayoshi ; Redis, Roxana S. ; Shah, Maitri Y. ; Zhang, Xinna ; Okugawa, Yoshinaga ; Jung, Eun Jung ; Tsirigos, Aristotelis ; Huang, Li ; Ferdin, Jana ; Gafà, Roberta ; Spizzo, Riccardo ; Nicoloso, Milena S. ; Paranjape, Anurag N. ; Shariati, Maryam ; Tiron, Aida ; Yeh, Jen Jen ; Teruel-Montoya, Raul ; Xiao, Lianchun ; Melo, Sonia A. ; Menter, David ; Jiang, Zhi Qin ; Flores, Elsa R. ; Negrini, Massimo ; Goel, Ajay ; Bar-Eli, Menashe ; Mani, Sendurai A. ; Liu, Chang Gong ; Lopez-Berestein, Gabriel ; Berindan-Neagoe, Ioana ; Esteller, Manel ; Kopetz, Scott ; Lanza, Giovanni ; Calin, George A. / N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration. In: Genome biology. 2017 ; Vol. 18, No. 1.
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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.",
author = "Isidore Rigoutsos and Lee, {Sang Kil} and Nam, {Su Youn} and Simone Anfossi and Barbara Pasculli and Martin Pichler and Yi Jing and Cristian Rodriguez-Aguayo and Telonis, {Aristeidis G.} and Simona Rossi and Cristina Ivan and {Catela Ivkovic}, Tina and Linda Fabris and Clark, {Peter M.} and Hui Ling and Masayoshi Shimizu and Redis, {Roxana S.} and Shah, {Maitri Y.} and Xinna Zhang and Yoshinaga Okugawa and Jung, {Eun Jung} and Aristotelis Tsirigos and Li Huang and Jana Ferdin and Roberta Gaf{\`a} and Riccardo Spizzo and Nicoloso, {Milena S.} and Paranjape, {Anurag N.} and Maryam Shariati and Aida Tiron and Yeh, {Jen Jen} and Raul Teruel-Montoya and Lianchun Xiao and Melo, {Sonia A.} and David Menter and Jiang, {Zhi Qin} and Flores, {Elsa R.} and Massimo Negrini and Ajay Goel and Menashe Bar-Eli and Mani, {Sendurai A.} and Liu, {Chang Gong} and Gabriel Lopez-Berestein and Ioana Berindan-Neagoe and Manel Esteller and Scott Kopetz and Giovanni Lanza and Calin, {George A.}",
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month = "5",
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language = "English",
volume = "18",
journal = "Genome Biology",
issn = "1474-7596",
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Rigoutsos, I, Lee, SK, Nam, SY, Anfossi, S, Pasculli, B, Pichler, M, Jing, Y, Rodriguez-Aguayo, C, Telonis, AG, Rossi, S, Ivan, C, Catela Ivkovic, T, Fabris, L, Clark, PM, Ling, H, Shimizu, M, Redis, RS, Shah, MY, Zhang, X, Okugawa, Y, Jung, EJ, Tsirigos, A, Huang, L, Ferdin, J, Gafà, R, Spizzo, R, Nicoloso, MS, Paranjape, AN, Shariati, M, Tiron, A, Yeh, JJ, Teruel-Montoya, R, Xiao, L, Melo, SA, Menter, D, Jiang, ZQ, Flores, ER, Negrini, M, Goel, A, Bar-Eli, M, Mani, SA, Liu, CG, Lopez-Berestein, G, Berindan-Neagoe, I, Esteller, M, Kopetz, S, Lanza, G & Calin, GA 2017, 'N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration', Genome biology, vol. 18, no. 1, 98. https://doi.org/10.1186/s13059-017-1224-0

N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration. / Rigoutsos, Isidore; Lee, Sang Kil; Nam, Su Youn; Anfossi, Simone; Pasculli, Barbara; Pichler, Martin; Jing, Yi; Rodriguez-Aguayo, Cristian; Telonis, Aristeidis G.; Rossi, Simona; Ivan, Cristina; Catela Ivkovic, Tina; Fabris, Linda; Clark, Peter M.; Ling, Hui; Shimizu, Masayoshi; Redis, Roxana S.; Shah, Maitri Y.; Zhang, Xinna; Okugawa, Yoshinaga; Jung, Eun Jung; Tsirigos, Aristotelis; Huang, Li; Ferdin, Jana; Gafà, Roberta; Spizzo, Riccardo; Nicoloso, Milena S.; Paranjape, Anurag N.; Shariati, Maryam; Tiron, Aida; Yeh, Jen Jen; Teruel-Montoya, Raul; Xiao, Lianchun; Melo, Sonia A.; Menter, David; Jiang, Zhi Qin; Flores, Elsa R.; Negrini, Massimo; Goel, Ajay; Bar-Eli, Menashe; Mani, Sendurai A.; Liu, Chang Gong; Lopez-Berestein, Gabriel; Berindan-Neagoe, Ioana; Esteller, Manel; Kopetz, Scott; Lanza, Giovanni; Calin, George A.

In: Genome biology, Vol. 18, No. 1, 98, 24.05.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

AU - Rigoutsos, Isidore

AU - Lee, Sang Kil

AU - Nam, Su Youn

AU - Anfossi, Simone

AU - Pasculli, Barbara

AU - Pichler, Martin

AU - Jing, Yi

AU - Rodriguez-Aguayo, Cristian

AU - Telonis, Aristeidis G.

AU - Rossi, Simona

AU - Ivan, Cristina

AU - Catela Ivkovic, Tina

AU - Fabris, Linda

AU - Clark, Peter M.

AU - Ling, Hui

AU - Shimizu, Masayoshi

AU - Redis, Roxana S.

AU - Shah, Maitri Y.

AU - Zhang, Xinna

AU - Okugawa, Yoshinaga

AU - Jung, Eun Jung

AU - Tsirigos, Aristotelis

AU - Huang, Li

AU - Ferdin, Jana

AU - Gafà, Roberta

AU - Spizzo, Riccardo

AU - Nicoloso, Milena S.

AU - Paranjape, Anurag N.

AU - Shariati, Maryam

AU - Tiron, Aida

AU - Yeh, Jen Jen

AU - Teruel-Montoya, Raul

AU - Xiao, Lianchun

AU - Melo, Sonia A.

AU - Menter, David

AU - Jiang, Zhi Qin

AU - Flores, Elsa R.

AU - Negrini, Massimo

AU - Goel, Ajay

AU - Bar-Eli, Menashe

AU - Mani, Sendurai A.

AU - Liu, Chang Gong

AU - Lopez-Berestein, Gabriel

AU - Berindan-Neagoe, Ioana

AU - Esteller, Manel

AU - Kopetz, Scott

AU - Lanza, Giovanni

AU - Calin, George A.

PY - 2017/5/24

Y1 - 2017/5/24

N2 - 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.

AB - 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.

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U2 - 10.1186/s13059-017-1224-0

DO - 10.1186/s13059-017-1224-0

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