The pyknon-containing N-BLR is a novel modulator of the epithelial-to-mesenchymal-transition process and of the apoptotic pathway in colorectal cancer
We discovered a new lncRNA, N-BLR. We showed that N-BLR plays key roles in the context of colorectal cancer (CRC), and that its abundance is associated with tumor stage, invasion potential, and overall patient survival 1. The importance of N-BLR for the clinical context was validated through independent cohorts of CRC patients making it a potential novel biomarker for this disease.
A key element to the mechanistic involvement of N-BLR in cellular processes is a 20 nt pyknon motif 3 near its 3′ end. We showed that targeted deletion of the pyknon affected colony formation, invasion, and migration. We also found several more pyknon-containing loci whose expression correlates with the overall survival of CRC patients. Parallel experiments with a custom-designed pyknon microarray that probed hundreds of pyknon-containing regions of the genome showed evidence of controlled transcription that was both tissue-specific and disease-specific. Because pyknons are primate-specific sequences 3,4,5 the findings suggest the possibility that these motifs could herald a novel class of biomarkers and therapeutic targets.
For a list of human and mouse pyknons and their genomic locations visit our pyknon page.
- 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. N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration. Genome Biol. 2017;18 (1):98. doi: 10.1186/s13059-017-1224-0. PubMed PMID:28535802 PubMed Central PMC5442648.
- Primate-specific long non-codingRNAs and the cancer link, BioMed Central blog
- Rigoutsos, I, Huynh, T, Miranda, K, Tsirigos, A, McHardy, A, Platt, D. Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes. Proc. Natl. Acad. Sci. U.S.A. 2006;103 (17):6605-10. doi: 10.1073/pnas.0601688103. PubMed PMID:16636294 PubMed Central PMC1447521.
- Tsirigos, A, Rigoutsos, I. Human and mouse introns are linked to the same processes and functions through each genome’s most frequent non-conserved motifs. Nucleic Acids Res. 2008;36 (10):3484-93. doi: 10.1093/nar/gkn155. PubMed PMID:18450818 PubMed Central PMC2425492.
- Rigoutsos, I. Short RNAs: how big is this iceberg?. Curr. Biol. 2010;20 (3):R110-3. doi: 10.1016/j.cub.2009.12.036. PubMed PMID:20144771 .