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Article

Many Different LINE-1 Retroelements Are Activated in Bladder Cancer

1
Department of Urology, Medical Faculty, Heinrich Heine University, 40225 Dusseldorf, Germany
2
Institute of Pathology, Medical Faculty, Heinrich Heine University, 40225 Dusseldorf, Germany
3
Biological and Medical Research Center (BMFZ), Heinrich Heine University, 40225 Dusseldorf, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9433; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249433
Received: 27 October 2020 / Revised: 4 December 2020 / Accepted: 7 December 2020 / Published: 11 December 2020
(This article belongs to the Special Issue Molecular Research on Urology 2.0)
Human genomes contain about 100,000 LINE-1 (L1) retroelements, of which more than 100 are intact. L1s are normally tightly controlled by epigenetic mechanisms, which often fail in cancer. In bladder urothelial carcinoma (UC), particularly, L1s become DNA-hypomethylated, expressed and contribute to genomic instability and tumor growth. It is, however, unknown which individual L1s are activated. Following RNA-immunoprecipitation with a L1-specific antibody, third generation nanopore sequencing detected transcripts of 90 individual elements in the VM-Cub-1 UC line with high overall L1 expression. In total, 10 L1s accounted for >60% of the reads. Analysis of five specific L1s by RT-qPCR revealed generally increased expression in UC tissues and cell lines over normal controls, but variable expression among tumor cell lines from bladder, prostate and testicular cancer. Chromatin immunoprecipitation demonstrated active histone marks at L1 sequences with increased expression in VM-Cub-1, but not in a different UC cell line with low L1 expression. We conclude that many L1 elements are epigenetically activated in bladder cancer in a varied pattern. Our findings indicate that expression of individual L1s is highly heterogeneous between and among cancer types. View Full-Text
Keywords: LINE-1 retroelements; urothelial carcinoma; histone modifications; RNA immunoprecipitation; nanopore sequencing; chromatin immunoprecipitation LINE-1 retroelements; urothelial carcinoma; histone modifications; RNA immunoprecipitation; nanopore sequencing; chromatin immunoprecipitation
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MDPI and ACS Style

Whongsiri, P.; Goering, W.; Lautwein, T.; Hader, C.; Niegisch, G.; Köhrer, K.; Hoffmann, M.J.; Schulz, W.A. Many Different LINE-1 Retroelements Are Activated in Bladder Cancer. Int. J. Mol. Sci. 2020, 21, 9433. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249433

AMA Style

Whongsiri P, Goering W, Lautwein T, Hader C, Niegisch G, Köhrer K, Hoffmann MJ, Schulz WA. Many Different LINE-1 Retroelements Are Activated in Bladder Cancer. International Journal of Molecular Sciences. 2020; 21(24):9433. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249433

Chicago/Turabian Style

Whongsiri, Patcharawalai; Goering, Wolfgang; Lautwein, Tobias; Hader, Christiane; Niegisch, Günter; Köhrer, Karl; Hoffmann, Michèle J.; Schulz, Wolfgang A. 2020. "Many Different LINE-1 Retroelements Are Activated in Bladder Cancer" Int. J. Mol. Sci. 21, no. 24: 9433. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249433

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