scholarly journals Identification of Blut, a Novel Long-Noncoding RNA Differentially Expressed in Burkitt Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3875-3875
Author(s):  
Jessica I Hoell ◽  
Kunal Das Mahapatra ◽  
Kebria Hezaveh ◽  
Andreas Kloetgen ◽  
Stephan Bernhart ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Nuclear Localization ◽  
Burkitt Lymphoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Differentially Expressed ◽  
Comprehensive Cancer Center ◽  
Non Coding Rnas ◽  
Coding Potential

Abstract The class of the so-called long non-coding RNAs (lncRNAs) is defined by their lacking coding potential and their length of more than 200 nucleotides. LncRNAs are readily detected in transcriptome analysis but have so far not been characterized or catalogued exhaustively. Although lncRNAs make up a major portion of the mammalian non-coding transcriptome, it is challenging to predict their functions due to their diversity in terms of size, sequence and biogenesis. However, several lncRNAs have already been shown to be involved in crucial cellular processes such as imprinting, regulation of cell proliferation and cellular differentiation. Their mode of action generally involves epigenetic modifications as well as transcriptional and post-transcriptional regulation. Within the ICGC (International Cancer Genome Consortium)-MMML-Seq (Molecular Mechanisms in Malignant Lymphoma by Sequencing) Consortium, which aims at fully characterizing a total of 250 germinal center derived B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), we conducted a search for yet unidentified genes. We here report the identification of a novel transcript, which we have named BLUT (Burkitt Lymphoma Unknown Transcript). BLUT is highly expressed in BL, with only very low expression levels in FL and no detectable expression in DLBCL. It is around 1050 nucleotides long with splice evidence for three exons, whereby exons 1 and 3 are shared between all isoforms. BLUT represents a putative lncRNA since it lacks conserved protein domains and has a splice site conservation pattern typical of non-coding transcripts. Furthermore, it is predicted as non-coding by the software Coding Potential Calculator and there was not a single peptide match between a published peptide database (Human Proteome Map) and any potential BLUT peptide (all isoforms). Moreover, BLUT shares a high sequence identity with two (so far) uncharacterized non-coding RNAs (Pan Troglodyte, Chlorocebus sabeus). We tested a cell line panel (consisting of 16 different cell lines including non-lymphoma cell lines) for BLUT expression but could only detect it in the two BL cell lines Namalwa and Raji. Cellular fractionation experiments showed that BLUT is predominantly localized in the nucleus in both Namalwa and Raji. Overexpression of BLUT in SU-DHL-4 resulted in the identification of 222 differentially regulated genes (FDR < 0.05) with a logFC of ± 0.25, among which 49 genes had a logFC of ± 0.50. Several lymphoma relevant genes were part of this list including BIN1, CCL22, CCR7, EBI3, ID2, JAG1, NQO1, and RGS1. Given its nuclear localization, we currently perform chromatin isolation by RNA purification experiments to identify the genomic regions which BLUT binds to. In combination with our overexpression data this will allow further insights into the functions of BLUT. In summary, we have identified a novel long-noncoding RNA termed BLUT, which is differentially expressed between lymphoma subtypes with a high expression in Burkitt lymphoma. Overexpression of BLUT resulted in the deregulation of several genes with known roles in lymphomagenesis. Given its predominantly nuclear localization, we are currently investigating its functions on chromatin regulation. (Supported by BMBF through 01KU1002A-J and by the Duesseldorf School of Oncology (funded by the Comprehensive Cancer Center Duesseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf)) Disclosures Truemper: Amgen, roche, Mundipharma: Research Funding; Sandoz, Celgene, AMGEN, Nordic Nanovector: Other: Advisory board.

scholarly journals Long Noncoding RNA SNHG1 Regulates LMNB2 Expression by Sponging miR-326 and Promotes Cancer Growth in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Wentao Mu ◽  
Lingyu Guo ◽  
Yang Liu ◽  
Hui Yang ◽  
Shanglei Ning ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Tumor Proliferation ◽  
Nude Mouse Model

ObjectiveThe purpose of the study is to explore the potential competing endogenous RNA (ceRNA) network and investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in hepatocellular carcinoma (HCC) development.MethodsBy analyzing the data of HCC in The Cancer Genome Atlas (TCGA) database, we included differentially expressed lncRNA and microRNA (miRNA) profiles and constructed ceRNA networks related to the prognosis of HCC patients. qRT-PCR, Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell assay, and the nude mouse model were employed to test the effects of SNHG1 and LMNB2 on tumor proliferation and growth in vitro and in vivo.ResultsIn the study, we identified 115 messenger RNAs (mRNAs), 12 lncRNAs, and 37 miRNAs by intersecting differentially expressed genes (DEGs) in TCGA and StarBase databases. Then, SNHG1–miR-326–LMNB2 pathway came into notice after further survival analysis and hub gene screening. Our results showed that SNHG1 expression was upregulated significantly in HCC tissues and cell lines. Downregulation of both LMNB2, the target of miR-326 in HCC, and SNHG1 inhibited tumor proliferation and growth in vitro and in vivo. Furthermore, SNHG1 could regulate LMNB2 expression through binding to miR-326 in HCC cell lines.ConclusionSNHG1 is a promising prognostic factor in HCC, and the SNHG1–miR-326–LMNB2 axis may be a potential therapeutic target for HCC.

scholarly journals Transcriptome-wide Profiling of Cerebral Cavernous Malformations Patients Reveal Important Long noncoding RNA molecular signatures

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Santhilal Subhash ◽  
Norman Kalmbach ◽  
Florian Wegner ◽  
Susanne Petri ◽  
Torsten Glomb ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Vascular Malformations ◽  
Cerebrovascular Disorders ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Low Flow ◽  
Pcr Analysis ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Non Coding Rnas

AbstractCerebral cavernous malformations (CCMs) are low-flow vascular malformations in the brain associated with recurrent hemorrhage and seizures. The current treatment of CCMs relies solely on surgical intervention. Henceforth, alternative non-invasive therapies are urgently needed to help prevent subsequent hemorrhagic episodes. Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the role of lncRNAs in cerebrovascular disorders, their identification in CCMs pathology remains unknown. The objective of the current study was to identify lncRNAs associated with CCMs pathogenesis using patient cohorts having 10 CCM patients and 4 controls from brain. Executing next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identified 1,967 lncRNAs and 4,928 protein coding genes (PCGs) to be differentially expressed in CCMs patients. Among these, we selected top 6 differentially expressed lncRNAs each having significant correlative expression with more than 100 differentially expressed PCGs. The differential expression status of the top lncRNAs, SMIM25 and LBX2-AS1 in CCMs was further confirmed by qRT-PCR analysis. Additionally, gene set enrichment analysis of correlated PCGs revealed critical pathways related to vascular signaling and important biological processes relevant to CCMs pathophysiology. Here, by transcriptome-wide approach we demonstrate that lncRNAs are prevalent in CCMs disease and are likely to play critical roles in regulating important signaling pathways involved in the disease progression. We believe, that detailed future investigations on this set of identified lncRNAs can provide useful insights into the biology and, ultimately, contribute in preventing this debilitating disease.

CD22 Cross-Linking Generates B-Cell Antigen Receptor-Independent Signals That Activate the JNK/SAPK Signaling Cascade

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1382-1392 ◽  
Author(s):  
Joseph M. Tuscano ◽  
Agostino Riva ◽  
Salvador N. Toscano ◽  
Thomas F. Tedder ◽  
John H. Kehrl
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Burkitt Lymphoma ◽  
B Cell Antigen Receptor ◽  
Erk Activation ◽  
Cell Antigen ◽  
Bcr Signaling ◽  
Burkitt Lymphoma Cell

Abstract CD22 is a B-cell–specific adhesion molecule that modulates BCR-mediated signal transduction. Ligation of human CD22 with monoclonal antibodies (MoAbs) that block the ligand binding site triggers rapid tyrosine phosphorylation of CD22 and primary B-cell proliferation. Because extracellular signal-regulated kinases (ERKs) couple upstream signaling pathways to gene activation and are activated by B-cell antigen receptor (BCR) signaling, we examined whether CD22 ligation also activated ERKs and/or modified BCR-induced ERK activation. Ligation of CD22 on either primary B cells or B-cell lines failed to significantly activate the mitogen activated protein kinase (MAPK) ERK-2, but did activate the stress-activated protein kinases (SAPKs; c-jun NH2-terminal kinases or JNKs). In contrast, BCR ligation resulted in ERK-2 activation without significant SAPK activation. Concurrent ligation of CD22 and BCR enhanced BCR-mediated ERK-2 activation without appreciably modulating CD22-induced SAPK activation. Consistent with its induction of SAPK activity, there was a marked increase in nuclear extracts of activator protein-1 (AP-1) and c-jun levels within 2 hours of exposure of primary B cells to the CD22 MoAb. Despite their differences in ERK activation, both CD22 and BCR ligation triggered several Burkitt lymphoma cell lines to undergo apoptosis, and the 2 stimuli together induced greater cell death than either signal alone. The pro-apoptotic effects were CD22-blocking MoAb-specific and dose-dependent. Examination of expression levels of Bcl-2 protoncogene family members (Bcl-2, Bcl-xL, Mcl-1, and Bax) showed a downregulation of Bcl-xL and Mcl-1 after CD22 ligation. This study provides a plausible mechanism to explain how CD22 and BCR signaling can costimulate B-cell proliferation and induce apoptosis in Burkitt lymphoma cell lines.

scholarly journals Global Long Noncoding RNA and mRNA Expression Changes between Prenatal and Neonatal Lung Tissue in Pigs

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 443 ◽  
Author(s):  
Long Jin ◽  
Silu Hu ◽  
Teng Tu ◽  
Zhiqing Huang ◽  
Qianzi Tang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Lung Tissue ◽  
Long Noncoding Rna ◽  
Lung Development ◽  
Noncoding Rna ◽  
Differentially Expressed ◽  
P Value ◽  
Distal Lung ◽  
Neonatal Lungs

Lung tissue plays an important role in the respiratory system of mammals after birth. Early lung development includes six key stages, of which the saccular stage spans the pre- and neonatal periods and prepares the distal lung for alveolarization and gas-exchange. However, little is known about the changes in gene expression between fetal and neonatal lungs. In this study, we performed transcriptomic analysis of messenger RNA (mRNA) and long noncoding RNA (lncRNA) expressed in the lung tissue of fetal and neonatal piglets. A total of 19,310 lncRNAs and 14,579 mRNAs were identified and substantially expressed. Furthermore, 3248 mRNAs were significantly (FDR-adjusted p value ≤ 0.05, FDR: False Discovery Rate) differentially expressed and were mainly enriched in categories related to cell proliferation, immune response, hypoxia response, and mitochondrial activation. For example, CCNA2, an important gene involved in the cell cycle and DNA replication, was upregulated in neonatal lungs. We also identified 452 significantly (FDR-adjusted p value ≤ 0.05) differentially expressed lncRNAs, which might function in cell proliferation, mitochondrial activation, and immune response, similar to the differentially expressed mRNAs. These results suggest that differentially expressed mRNAs and lncRNAs might co-regulate lung development in early postnatal pigs. Notably, the TU64359 lncRNA might promote distal lung development by up-regulating the heparin-binding epidermal growth factor-like (HB-EGF) expression. Our research provides basic lung development datasets and will accelerate clinical researches of newborn lung diseases with pig models.

scholarly journals Long noncoding RNA PVT1 promotes tumor growth and predicts poor prognosis in patients with diffuse large B‐cell lymphoma

2020 ◽  
Vol 40 (10) ◽  
pp. 551-555
Author(s):  
Ruifeng Yang ◽  
Tingting Shao ◽  
Manmei Long ◽  
Yongheng Shi ◽  
Qiang Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
B Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Expression of ZNF695 Transcript Variants in Childhood B-Cell Acute Lymphoblastic Leukemia

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 716 ◽  
Author(s):  
Rosa ◽  
Villegas-Ruíz ◽  
Caballero-Palacios ◽  
Pérez-López ◽  
Murata ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Alternative Transcript ◽  
Human Transcriptome ◽  
Transcript Variants ◽  
Cell Acute Lymphoblastic Leukemia

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for 2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.

Long Non-Coding RNAs Are Commonly Deregulated In Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 628-628
Author(s):  
Masoumeh Tayari ◽  
Klaas Kok ◽  
Gertrud Kortman ◽  
Jantine Sietzema ◽  
Debora de Jong ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Differential Expression ◽  
Potential Function ◽  
Expression Pattern ◽  
Differentially Expressed ◽  
Lncrna Expression ◽  
Non Coding Rnas ◽  
B Cell Subsets

Abstract Hodgkin’s lymphoma (HL) is a B-cell neoplasm characterized by a minority of neoplastic cells within an extensive inflammatory background. Long non-coding RNAs (lncRNAs) have diverse roles in transcriptional, posttranscriptional and epigenetic mechanisms in normal cell physiology. Deregulation of lncRNA expression has been implicated in a number of cancers. Up to date it is unclear to what extent lncRNAs are involved in the pathogenesis of Hodgkin lymphoma (HL). We designed a custom made microarray based on a published lncRNA catalog of 10,509 lncRNA loci (Cabili et al., 2011). The array also contains probes for all protein coding genes allowing simultaneous detection of the lncRNA and mRNA expression pattern. We analyzed 6 HL cell lines and three samples of purified tonsillar naive, germinal center (GC) and memory B cells. To get more insight into the potential function of individual differentially expressed lncRNAs we determined lncRNA enrichment in cytoplasmic and nuclear fractions of two HL cell lines. Furthermore, we studied to what extent lncRNAs are enriched in the Argonaute 2 (Ago2) containing complexes as an indication for interaction with miRNAs. In a comparison between the three different normal B-cell subsets, we observed 565 differentially expressed lncRNA probes. Overall, naive and memory B cell subsets showed a highly similar expression pattern while GC B cells showed a distinct lncRNA expression pattern. A significant differential expression between HL and normal GC B-cells was observed for 717 lncRNA probes. Interestingly, 109 of those overlap with the 565 lncRNAs differentially expressed between the normal B cell subsets. Differential expression for 4 in HL up and 2 downregulated lncRNAs was confirmed using qRT-PCR. To get a first indication about their potential function, we evaluated the subcellular location of the lncRNAs by comparing the abundance in nuclear and cytoplasmic fractions relative to the total fraction. Overall, 26% of the expressed lncRNAs were consistently enriched in the nuclear fraction and 10% were predominantly enriched in the cytoplasmic fraction. Of the 717 differentially expressed lncRNAs 82 were consistently enriched in the nucleus and 16 in the cytoplasm. Our Ago2 pull-down experiments revealed that 9% of the mRNAs and 3% of the expressed lncRNAs are consistently enriched in Ago2 complexes. In total, we observed evidence for miRNA binding for 17 of the in HL differentially expressed lncRNAs. In conclusion, we identified a specific lncRNA expression pattern in GC B cells and observed for more than 700 lncRNAs a differentially expression pattern between HL and normal GC B-cells. For 98 lncRNAs we found a specific subcellular enrichment and for 17 we observed enrichment in the Ago2 fraction, indicative of miRNA-lncRNA interactions. Follow-up studies will determine to what extent these lncRNAs contribute to the pathogenesis of Hodgkin lymphoma. Disclosures: No relevant conflicts of interest to declare.

CD22 Cross-Linking Generates B-Cell Antigen Receptor-Independent Signals That Activate the JNK/SAPK Signaling Cascade

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1382-1392
Author(s):  
Joseph M. Tuscano ◽  
Agostino Riva ◽  
Salvador N. Toscano ◽  
Thomas F. Tedder ◽  
John H. Kehrl
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Burkitt Lymphoma ◽  
B Cell Antigen Receptor ◽  
Erk Activation ◽  
Cell Antigen ◽  
Bcr Signaling ◽  
Burkitt Lymphoma Cell

CD22 is a B-cell–specific adhesion molecule that modulates BCR-mediated signal transduction. Ligation of human CD22 with monoclonal antibodies (MoAbs) that block the ligand binding site triggers rapid tyrosine phosphorylation of CD22 and primary B-cell proliferation. Because extracellular signal-regulated kinases (ERKs) couple upstream signaling pathways to gene activation and are activated by B-cell antigen receptor (BCR) signaling, we examined whether CD22 ligation also activated ERKs and/or modified BCR-induced ERK activation. Ligation of CD22 on either primary B cells or B-cell lines failed to significantly activate the mitogen activated protein kinase (MAPK) ERK-2, but did activate the stress-activated protein kinases (SAPKs; c-jun NH2-terminal kinases or JNKs). In contrast, BCR ligation resulted in ERK-2 activation without significant SAPK activation. Concurrent ligation of CD22 and BCR enhanced BCR-mediated ERK-2 activation without appreciably modulating CD22-induced SAPK activation. Consistent with its induction of SAPK activity, there was a marked increase in nuclear extracts of activator protein-1 (AP-1) and c-jun levels within 2 hours of exposure of primary B cells to the CD22 MoAb. Despite their differences in ERK activation, both CD22 and BCR ligation triggered several Burkitt lymphoma cell lines to undergo apoptosis, and the 2 stimuli together induced greater cell death than either signal alone. The pro-apoptotic effects were CD22-blocking MoAb-specific and dose-dependent. Examination of expression levels of Bcl-2 protoncogene family members (Bcl-2, Bcl-xL, Mcl-1, and Bax) showed a downregulation of Bcl-xL and Mcl-1 after CD22 ligation. This study provides a plausible mechanism to explain how CD22 and BCR signaling can costimulate B-cell proliferation and induce apoptosis in Burkitt lymphoma cell lines.

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