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The relationship between lncRNA and its targets on the hematological diseases. The inner red part of the circle is the name of hematologic disease. The middle blue part of the circle is the name of lncRNAs. The outer yellow part of the circle is the target of hematologic disease regulated by lncRNAs. lncRNAs: Long non-coding RNAs; APL: Acute promyelocytic leukemia; AML: Acute myeloid leukemia; CML: Chronic myeloid leukemia; B-ALL: B-cell acute lymphocytic leukemia; CLL: Chronic leukemia; DLBCL: Diffuse large B-cell lymphoma; NHL: Non-Hodgkin lymphoma; HL: Hodgkin lymphoma; MM: Multiple myeloma; MDS: Myelodysplastic syndromes; AA: Aplastic anemia; NEAT1: Nuclear paraspeckle assembly transcript 1; RUNXOR: RUNX1 overlapping RNA; PLIN2: Perilipin 2; lncRNA-BGL3: LncRNA-BetaGlobinLocus 3; HOTAIR: Hox transcript antisense RNA; HULC: Highly up-regulated in liver cancer; UCA1: Urothelial carcinoma-associated 1; LUNAR1: LeUkemia-induced non-coding activator RNA; BALR-2: B-ALL-associated long RNA-2; CRNDE: Colorectal neoplasia differentially expressed; MIAT: Myocardial infarction-associated transcript; MINCR: MYC-induced lncRNA; PANDA: P21-associated ncRNA DNA damage activated; MEG3: Maternally expressed gene 3; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; RUNX1: Runt-related transcription factor 1; IGF1R: Insulin-like growth factor-1 receptor; HDAC: Histone deacetylase; CEBPA: CCAAT/enhancer-binding protein-a; GSK-3: Glycogen synthase kinase-3; PTEN: Gene of phosphate and tension homology deleted on chromosome 10; EZH2: Enhancer of zeste homolog 2; MAPK/ERK: Mitogen-activated protein kinase/extracellular regulated protein kinases; BMP4: Bone morphogenetic protein 4; LTBP3: Latent-transforming growth factor beta-binding protein 3; FGF1: Fibroblast growth factor 1.
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Objective:
Long non-coding RNAs (lncRNAs) have recently been discovered and are increasingly recognized as vital components of modern molecular biology. Accumulating evidence shows that lncRNAs have emerged as important mediators in diverse biological processes such as cell differentiation, pluripotency, and tumorigenesis, while the function of ln...
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Context 1
... addition to the normal hematopoietic process regulated by a variety of lncRNAs, abnormal interference of lncRNA regulation also inevitably leads to hematopoietic dysfunction, mainly in the occurrence of leukemia, lymphoma, and myeloma. At present, several lncRNAs related to hematological malignancies have been identified and summarized in the following sections [ Table 2 and Figure 3]. ...
Citations
... The interplay of environmental stimuli and intracellular regulatory processes plays a vital role in the process of hematopoietic lineage development. It is now becoming clear that lineagespecific lncRNAs play a significant role in controlling gene expression during hematopoiesis [54]. ...
... About 100 lncRNAs have been found to control different elements of vertebrate cell biology and development overall, according to functional investigations. This suggests that this class of molecules performs a wide range of important roles [54]. ...
... Gene regulation affects the formation and function of B lymphocytes, which are the main players in the immunological humoral response [66]. Scientists have discovered a number of lncRNAs, including lncRNA-CSR and CRNDE, that are important in the growth, activation, proliferation, and differentiation of B cells using RNA-seq and de novo transcript assembly [54]. ...
Transcripts longer than 200 nucleotides that are not translated into proteins are known as long non-coding RNAs, or lncRNAs. Now, they are becoming more significant as important regulators of gene expression, and as a result, of many biological processes in both healthy and pathological circumstances, such as blood malignancies. Through controlling alternative splicing, transcription, and translation at the post-transcriptional level, lncRNAs have an impact on the expression of genes. In multiple myeloma (MM), the majority of lncRNAs is elevated and promotes the proliferation, adhesion, drug resistance and invasion of MM cells by blocking apoptosis and altering the tumor microenvironment (TME). To control mRNA splicing, stability, and translation, they either directly attach to the target mRNA or transfer RNA-binding proteins (RBPs). By expressing certain miRNA-binding sites that function as competitive endogenous RNAs (ceRNAs), most lncRNAs mimic the actions of miRNAs. Here, we highlight lncRNAs role in the MM pathogenesis with emphasize on their capacity to control the molecular mechanisms known as “hallmarks of cancer,” which permit earlier tumor initiation and progression and malignant cell transformation.
... However, the characterization and mechanistic exploration of these lncRNAs are still in their infancy. 45 LncRNA15691, a 361-nt-long RNA located on chromosome 9, has not been annotated or documented in normal or cancer cells. The results of this study revealed that lncRNA15691 was upregulated in T-ALL, especially in CCR9 high T-ALL cells, and was located in both the cytoplasm and nucleus. ...
Our previous studies demonstrated that CCR9 plays an important role in several aspects of T-cell acute lymphoblastic leukemia progression and that CCR9 is a potential therapeutic target. However, the underlying mechanism that regulates CCR9 expression remains incompletely understood. In this study, bioinformatics analysis and validation in clinical samples revealed the lncRNA15691 to be positively correlated with CCR9 mRNA expression and significantly upregulated in T-cell acute lymphoblastic leukemia samples and CCR9high T-cell acute lymphoblastic leukemia cell lines. LncRNA15691, a previously uncharacterized lncRNA, was found to be located in both the cytoplasm and the nucleus via fluorescence in situ hybridization assay. In addition, lncRNA15691 upregulated the expression of CCR9 and was involved in T-cell acute lymphoblastic leukemia cell invasion. In vivo experiments showed that lncRNA15691 promoted leukemia cell homing/infiltration into the bone marrow, blood, and spleen, whereas the CCR9 ligand, CCL25, augmented the extramedullary infiltration of CCR9low leukemia cells overexpressing lncRNA15691 into blood, spleen, and liver. Subsequently, RNA protein pull-down assays, coupled with liquid chromatography–tandem mass spectrometry, were used to uncover potential lncRNA15691-interacting proteins, which were then validated by RNA immunoprecipitation. These mechanistic studies revealed that lncRNA15691 upregulated CCR9 expression via directly binding to and stabilizing MATR3 by inhibiting its nuclear degradation mediated by PKA. Collectively, our study revealed a novel mechanism of regulating CCR9 expression and implicated lncRNA15691 as a potential novel biomarker for T-cell acute lymphoblastic leukemia infiltration.
... Indicates poor prognosis in AML patients. [116][117][118] Circ-ANAPC7 (hsa_circ_101141): This circRNA is seen to sponge the miRNA-181 family. It results in proliferation of pathogenesis of AML. ...
The idea of functional non-coding RNAs is taking precedence over the previous notion which believed that they only comprise the auxiliary and junk material of the genome. Newer technologies and studies have proven their importance in regulating and affecting several cellular processes. One such area of research wherein their importance has started to take light is in cancer research, particularly leukemia. Myeloid leukemia is a blood malignancy birthed from mutations in hematopoiesis that disable myeloid progenitor cells from proper differentiation. This review will compile the most recent findings regarding the effects of these regulatory non-coding RNAs on the two types of myeloid leukemia. In particular, the effects of circular RNAs, micro RNAs and long non-coding RNAs, on the pathogenesis and proliferation of Acute and Chronic myeloid leukemia will be revealed in a molecular, cellular and prognostic light. The mechanisms of proliferation, gene-to-gene interactions and possible therapeutic effects will also be discussed. Finally, an understanding of the overall "goodness" and "badness" of these non-coding RNAs will be summarised. This review hopes to provide a platform for easy access to data regarding the current non-coding RNAs in myeloid leukemia, for faster and easier research. Finally, the review will summarize a few key players that have protagonistic and antagonistic functions, and those that regulate multiple pathways in leukemia simultaneously.
... LOC285758 controls proliferation of leukemia cell clones by increasing the expression of HDAC2. LOC285758 has been shown to be associated with an aggressive status and a poor prognosis of AML [12,13]. ...
Long non-coding RNAs are non-coding RNAs, which contribute to different biological processes. The expression of these RNAs alters in various diseases. This study aimed to compare the expression of long non-coding RNA genes in newly diagnosed patients with de novo acute myeloid leukemia and to evaluate their response to cytarabine-based treatment. In this cross-sectional study, approved by the Ethics Committee of Shiraz University of Medical Sciences (Shiraz, Iran), the expression of LOC285758, IRAIN, and HOTAIR was examined in de novo AML patients at Namazi Teaching Hospital during 2019-2020. The patients, treated with standard regimens, were compared with the controls, using quantitative real time- polymerase chain reaction assay. After whole blood samples were collected from the subjects, total RNA was extracted by Trizol reagent from whole blood. Next, cDNA was synthesized, and the expression levels of LOC285758, HOTAIR, and IRAIN were analyzed by RT-PCR assay, using SYBER Green Master Mix and 2 -ΔΔCt method. The results showed that the expression of LOC285758 was significantly upregulated in AML patients, compared to the controls (P< 0.001). After complete remission, the expression of LOC285758 was re-evaluated in patients. It was found that LOC285758 was significantly downregulated in de novo AML patients (P=0.001). The expression of HOTAIR, similar to IRAIN, did not change in de novo AML patients, whereas it was downregulated in patients with complete remission, compared to the controls. The present findings indicated that LOC285758 could discriminate AML patients from the healthy controls and indicate the patients’ response to treatment.
... Moreover, deregulated miRNAs have oncogenic and/or tumor suppressive functional roles [129]. In CML, miRNAs have been shown to act both as oncogenes and tumor suppressor genes [129][130][131][132][133]. Since circulating miRNAs can be detected in body fluids, this makes them ideal biomarkers for tumor diagnostics and progress monitoring [134]. ...
... In CML, miRNAs have been shown to act both as oncogenes and tumor suppressor genes [129][130][131][132][133]. Since circulating miRNAs can be detected in body fluids, this makes them ideal biomarkers for tumor diagnostics and progress monitoring [134]. Numerous long noncoding RNAs (lncRNAs) have been discovered recently and recognized as essential in gene regulation [133]. lncRNAs are >200 nt in length, transcribed via RNA polymerase II/ III, and weakly conserved [134]. ...
Chronic Myeloid Leukemia (CML) is a rare malignant proliferative disease of the hematopoietic system, whose molecular hallmark is the Philadelphia chromosome (Ph). The Ph chromosome originates an aberrant fusion gene with abnormal kinase activity, leading to the buildup of reactive oxygen species and genetic instability of relevance in disease progression. Several genetic abnormalities have been correlated with CML in the blast phase, including chromosomal aberrations and common altered genes. Some of these genes are involved in the regulation of cell apoptosis and proliferation, such as the epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), or Schmidt-Ruppin A-2 proto-oncogene (SRC); cell adhesion, e.g., catenin beta 1(CTNNB1); or genes associated to TGF-β, such as SKI like proto-oncogene (SKIL), transforming growth factor beta 1 (TGFB1) or transforming growth factor beta 2 (TGFB2); and TNF-α pathways, such as Tumor necrosis factor (TNFA) or Nuclear factor kappa B subunit 1 (NFKB1). The involvement of miRNAs in CML is also gaining momentum, where dysregulation of some critical miRNAs, such as miRNA-451 and miRNA-21, which have been associated to the molecular modulation of pathogenesis, progression of disease states, and response to therapeutics. In this review, the most relevant genomic alterations found in CML will be addressed.
... Lymphoid differentiation-related lncRNAs have been explored in recent years. 101 Tayari et al showed the dynamic regulation of lncRNA expression during B cell transition from naïve B cells to GC-B cells, resulting in memory B cells. 102 One study examined RNA-Seq data sets of DLBCL and identified 2632 novel, multi-exonic candidate lncRNAs expressed in more than one DLBCL tumor, most of which are not expressed in normal B cells. ...
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide. The molecular mechanisms underlying DLBCL have not been fully elucidated, and approximately 40% of patients who undergo standard chemoimmunotherapy still present with primary refractory disease or relapse. Non-coding RNAs (ncRNAs), a group of biomolecules functioning at the RNA level, are increasingly recognized as vital components of molecular biology. With the development of RNA-sequencing (RNA-Seq) technology, accumulating evidence shows that ncRNAs are important mediators of diverse biological processes such as cell proliferation, differentiation, and apoptosis. They are also considered promising biomarkers and better candidates than proteins and genes for the early recognition of disease onset, as they are associated with relative stability, specificity, and reproducibility. In this review, we provide the first comprehensive description of the current knowledge regarding three groups of ncRNAs—microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs)—focusing on their characteristics, molecular functions, as well as diagnostic and therapeutic potential in DLBCL. This review provides an exhaustive account for researchers to explore novel biomarkers for the diagnosis and prognosis of DLBCL and therapeutic targets.
The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs can serve as oncogenes or tumor suppressors depending on the target genes. In MM, miRNA disruption could result in abnormal gene expression responsible for cell growth, apoptosis, and other biological processes pertinent to cancer development. The dysregulated miRNAs inhibit the activity of tumor suppressor genes, contributing to disease progression. Nonetheless, several miRNAs are downregulated in MM and have been identified as gene regulators implicated in extracellular matrix remodeling and cell adhesion. miRNA depletion potentially facilitates the tumor advancement and resistance of therapeutic drugs. Additionally, lncRNAs are key regulators of numerous cellular processes, such as gene expression, chromatin remodeling, protein trafficking, and recently linked MM development. The lncRNAs are uniquely expressed and influence gene expression that supports MM growth, in addition to facilitating cellular proliferation and viability via multiple molecular pathways. miRNA and lncRNA alterations potentially result in anomalous gene expression and interfere with the regular functioning of MM. Thus, this review aims to highlight the dysregulation of these ncRNAs, which engender novel therapeutic modalities for the treatment of MM.
Keywords: multiple myeloma; pathogenesis; dysregulation; non-coding RNAs; microRNAs; long non-coding RNAs
Les longs ARNs non codants (lncRNAs) sont définis comme des transcrits ayant une taille supérieure à 200 nucléotides et dépourvus de potentiel codant. Longtemps considérés comme inutiles, leur étude récente a démontré qu’ils jouent un rôle important dans l’expression de nos gènes. On compte d’ailleurs de plus en plus d’exemples de ces lncRNAs dérégulés dans les cancers. Notre étude visait à évaluer l’existence de profils d’expression particuliers de lncRNAs au sein des leucémies aiguës myéloïdes à caryotype normal (LAM-CN), dont l’implication dans cette pathologie n’est que peu décrite. Le séquençage des ARNs que l’on a effectué sur une cohorte de 40 patients atteints de LAM-CN nous a permis de faire ressortir une signature minimale de 12 lncRNAs différentiellement exprimés chez les patients porteurs de la mutation dans le gène de la nucléophosmine (NPM1). Ces résultats ont été validés par RT-qPCR (Fluidigm) sur une cohorte indépendante composée de 134 nouveaux patients atteints de LAM-CN. Parmi cette signature, nous avons identifié un biomarqueur potentiel, le XLOC_109948, dont la faible expression est associée à un bon pronostic, particulièrement chez les patients NPM1 mutés. De plus, l’inhibition de ce lncRNA par transfection transitoire de gapmeRs dans une lignée cellulaire de LAM NPM1 muté augmente l’apoptose de ces cellules traitées à l’aracytine, suggérant un rôle du XLOC_109948 dans la sensibilité au traitement. Nous avons également caractérisé un autre lncRNA de la signature NPM1, baptisé LONA (LncRNA Overexpressed in NPM1-Mutated AML patients). Nous avons remarqué d’une part, que la mutation NPM1 induit une délocalisation nucléaire du lncRNA LONA, ce qui impacte ses fonctions cellulaires. Des stratégies perte et gain de fonctions ont montré que LONA aurait un rôle oncogénique en contexte de LAM NPM1 muté où il est impliqué in vitro et in vivo dans les processus de différentiation myéloïde et de croissance cellulaire en régulant l’expression de gènes cruciaux tels que THBS1, ASB2 ou MAFB. A l’inverse, la dérégulation de LONA en contexte de LAM NPM1 sauvage induit des effets opposés et suppresseurs de tumeurs, suggérant des régulations différentes en fonction du statut mutationnel de NPM1. D’autre part, le locus du lncRNA LONA est situé sur le chromosome 6 humain, au sein du cluster HIST1 codant des gènes des histones canoniques. Chez les patients NPM1 muté, l’expression du lncRNA LONA est inversement corrélée à celle de gènes voisins codant des histones. De manière cohérente, la diminution du lncRNA LONA dans notre lignée de LAM NPM1 muté est associée à une augmentation de l’expression de certaines des histones proximales du cluster. Par immunoprécipitation d’ARN, nous avons montré que LONA interagit avec le complexe de répression Polycomb (PRC2), suggérant sa contribution dans les régulations épigénétiques de la transcription des histones. De manière plus préliminaire, le lncRNA LONA pourrait également réguler l’étape de maturation des messagers des histones canoniques, en séquestrant telle une éponge moléculaire le snRNA U7, un petit ARN régulateur impliqué dans la maturation des extrémités 3’ des ARNs messagers des histones. L’ensemble de ces données suggère que les lncRNAs pourraient être considérés comme des biomarqueurs potentiels robustes, et apparaissent comme des acteurs clés dans le développement des leucémies aiguës myéloïdes.
Increasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.
