Identification of two unannotated miRNAs in classic Hodgkin lymphoma cell lines
Creators
- 1. 1. Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
- 2. 2. Interdisciplinary Center for Bioinformatics, Transcriptome Bioinformatics, University of Leipzig, Leipzig, Germany.
- 3. 3. Dr. Senckenberg Institute of Pathology, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
- 4. 4. Institut d'Investigacions Biomèdiques August Pi I Sunyer, IDIBAPS, Barcelona, Spain.
- 5. 5. Frankfurt Institute of Advanced Studies, Ruth-Moufang-Str. 1, 60438 Frankfurt am Main, Germany.
- 6. 10. Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany.
Description
MicroRNAs (miRNAs) are small non coding RNAs responsible for posttranscriptional regulation of gene expression. Even though almost 2000 precursors have been described so far, additional miRNAs are still being discovered in normal as well as malignant cells. Alike protein coding genes, miRNAs may acquire oncogenic properties in consequence of altered expression or presence of gain or loss of function mutations. In this study we mined datasets from miRNA expression profiling (miRNA-seq) of 7 classic Hodgkin Lymphoma (cHL) cell lines, 10 non-Hodgkin lymphoma (NHL) cell lines and 56 samples of germinal center derived B-cell lymphomas. Our aim was to discover potential novel cHL oncomiRs not reported in miRBase (release 22.1) and expressed in cHL cell lines but no other B-cell lymphomas. We identified six such miRNA candidates in cHL cell lines and verified the expression of two of them encoded at chr2:212678788-212678849 and chr5:168090507-168090561 (GRCh38). Interestingly, we showed that one of the validated miRNAs (located in an intron of the TENM2 gene) is expressed together with its host gene. TENM2 is characterized by hypomethylation and open chromatin around its TSS in cHL cell lines in contrast to NHL cell lines and germinal centre B-cells respectively. It indicates an epigenetic mechanism responsible for aberrant expression of both, the TENM2 gene and the novel miRNA in cHL cell lines.