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Genome Biol. 2017 May 24;18(1):98. doi: 10.1186/s13059-017-1224-0.

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

Author information

1
Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA. isidore.rigoutsos@jefferson.edu.
2
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Present address: Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
4
Gastroenterology, Department of Internal Medicine, Kyungpook National University Medical School, Daegu, Korea.
5
Present address: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
6
Present address: Division of Oncology, Medical University of Graz, Graz, Austria.
7
Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
8
Center for RNA interference and non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
9
Present address: Institute of Oncology Research (IOR), Research Division of the Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
10
Department of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croatia.
11
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
12
Present address: ProQR Therapeutics, Leiden, Netherlands.
13
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
14
Center for Gastrointestinal Research, and Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
15
Department of Surgery, School of Medicine, Gyeongsang National University, Jin-ju, South Korea.
16
Department of Pathology, NYU Langone Medical Center, New York, NY, 10016, USA.
17
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
18
Present address: Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
19
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
20
Present address: CRO, National Cancer Institute, 33081, Aviano, Italy.
21
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
22
Present address: National Cancer Institute, Bethesda, MD, USA.
23
Department of Medicine, Nassau University Medical Center, 2201 Hempstead Tpke, East Meadow, NY, 11554, USA.
24
Departments of Surgery and Pharmacology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
25
Present address: Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CIBEER (CB15/00055), Murcia, Spain.
26
Division of Quantitative Science, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
27
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, and Ipatimup - Institute of Pathology and Molecular Immunology of the University of Porto, 4200, Porto, Portugal.
28
Department of Pathology, Faculty of Medicine of Porto University, 4200-319, Porto, Portugal.
29
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
30
Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL, USA.
31
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Medfuture, Cluj-Napoca, Romania.
32
Research Center for Advanced Medicine - University of Medicine and Pharmacy "Iuliu Haţieganu", Cluj-Napoca, Romania.
33
Department of Functional Genomics, Proteomics and Experimental Pathology- The Oncology Institute " Prof Dr. Ion Chiricuta, Cluj-Napoca, Romania.
34
Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
35
Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain.
36
Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
37
Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
38
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. gcalin@mdanderson.org.
39
Center for RNA interference and non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. gcalin@mdanderson.org.

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.

KEYWORDS:

CLL; CRC; EMT; N-BLR; Non-coding RNA; Pyknons; Transcription; lncRNA; ncRNA

PMID:
28535802
PMCID:
PMC5442648
DOI:
10.1186/s13059-017-1224-0
[Indexed for MEDLINE]
Free PMC Article

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