Long Noncoding RNA Expression Profiling in Normal B-Cell Subsets and Hodgkin Lymphoma Reveals Hodgkin and Reed-Sternberg Cell–Specific Long Noncoding RNAs

Abstract

Hodgkin lymphoma (HL) is a malignancy of germinal center (GC) B-cell origin. To explore the role of long noncoding RNAs (lncRNAs) in HL, we studied lncRNA expression patterns in normal B-cell subsets, HL cell lines, and tissues. Naive and memory B cells showed a highly similar lncRNA expression pattern, distinct from GC-B cells. Significant differential expression between HL and normal GC-B cells was observed for 475 lncRNA loci. For two validated lncRNAs, an enhanced expression was observed in HL, diffuse large B-cell lymphoma, and lymphoblastoid cell lines. For a third lncRNA, increased expression levels were observed in HL and part of Burkitt lymphoma cell lines. RNA fluorescence in situ hybridization on primary HL tissues revealed a tumor cell-specific expression pattern for all three lncRNAs. A potential cis-regulatory role was observed for 107 differentially expressed lncRNA-mRNA pairs localizing within a 60-kb region. Consistent with a cis-acting role, we showed a preferential nuclear localization for two selected candidates. Thus, we showed dynamic lncRNA expression changes during the transit of normal B cells through the GC reaction and widely deregulated lncRNA expression patterns in HL. Three lncRNAs showed a tumor cell-specific expression pattern in HL tissues and might therefore be of value as a biomarker.

Non-Coding RNAs in Hodgkin Lymphoma

“…The authors detected 9955 lncRNAs in HL cell lines (DEV, L540, SUP-HD1, L1236, KM-H2, and L428) [66]. The unsupervised hierarchical cluster analysis using the 401 lncRNA differentially expressed in GC vs. naïve and memory B cells, showed that HL cell lines had a differential expression pattern close to GC B cells.…”

“…Moreover, RNA-FISH of the three lncRNAs in four cHL cases revealed a tumor cell-specific staining. The authors suggested that LINC00461 and FLJ42351 could act as cis-regulatory elements for MEFC2 and SLC20A1, respectively [66]. …”

MicroRNA High Throughput Loss-of-Function Screening Reveals an Oncogenic Role for miR-21-5p in Hodgkin Lymphoma

“…7C and Table 1). Analysis of our previously published microarray data in GC-B cells and cHL cell lines [29], showed a significantly decreased gene expression level in cHL cell lines compared to GC-B cells for 4 genes i.e. BTG2 (B-cell translocation gene 2), PELI1 (E3 Ubiquitin-Protein Ligase Pellino Homolog 1), TIAM1 (T-Cell Lymphoma Invasion And Metastasis 1) and SMAD7, whereas 1 gene, i.e.…”

Hodgkin Lymphoma Cells Have a Specific Long Noncoding RNA Expression Pattern

“…2,3 For example, tumor-specific expression and aberrant expression of lncRNAs compared with normal tissue has been identified in prostate cancer (PCA3 and PCGEM1), 4,5 lung cancer (MALAT1), 6 breast cancer (HOTAIR), 7 and colon cancer (PINT). 8 In this issue of The American Journal of Pathology, a novel study by Tayari et al 9 compared the expression profiles of lncRNAs in normal B-cell subsets [naïve, germinal center (GC), memory B-cells] and Hodgkin lymphoma (HL) cells. The study identified distinct expression patterns of lncRNAs among the normal B-cells and between normal B-cells and HL cells.…”

“…Indeed, molecular pathways that regulate normal B-cell development are also involved in pathogenesis of lymphomas, and several malignant lymphomas originate from distinct stages of normal Bcell development. 17 The study by Tayari et al 9 gave insight toward the identification of a specific lncRNA expression pattern for normal B-cells as well as for HL B-cells. It was shown that there is a dynamic regulation of lncRNA and mRNA expression during the normal B-cell maturation with an expression change of 251 lncRNA loci during the transition from naïve to GC-B cells and a reversion toward levels comparable to naïve B-cells during the differentiation to memory B-cells.…”