NEAT1 Long Isoform Is Highly Expressed in Chronic Lymphocytic Leukemia Irrespectively of Cytogenetic Groups or Clinical Outcome

Abstract

The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in chronic lymphocytic leukemia (CLL) are still open questions. Herein, we investigated the significance of the lncRNA NEAT1 in CLL. We examined NEAT1 expression in 310 newly diagnosed Binet A patients, in normal CD19+ B-cells, and other types of B-cell malignancies. Although global NEAT1 expression level was not statistically different in CLL cells compared to normal B cells, the median ratio of NEAT1_2 long isoform and global NEAT1 expression in CLL samples was significantly higher than in other groups. NEAT1_2 was more expressed in patients carrying mutated IGHV genes. Concerning cytogenetic aberrations, NEAT1_2 expression in CLL with trisomy 12 was lower with respect to patients without alterations. Although global NEAT1 expression appeared not to be associated with clinical outcome, patients with the lowest NEAT1_2 expression displayed the shortest time to first treatment; however, a multivariate regression analysis showed that the NEAT1_2 risk model was not independent from other known prognostic factors, particularly the IGHV mutational status. Overall, our data prompt future studies to investigate whether the increased amount of the long NEAT1_2 isoform detected in CLL cells may have a specific role in the pathology of the disease.

m(6)A Modification of lncRNA NEAT1 Regulates Chronic Myelocytic Leukemia Progression via miR-766-5p/CDKN1A Axis

“…However, few research studies focus on the upstream regulation of lncRNAs. Recently, m6A modification has become an epigenetic hot point ( 11 ). Therefore, in the current study, we explored the regulatory axis of NEAT1 in CML and ulteriorly investigated the upstream modification of NEAT1.…”

“…lncRNA nuclear enriched abundant transcript 1 (NEAT1) is an essential structural component of the subnuclear structure paraspeckle (8) and is closely related to malignant tumors and innate immunity (9). NEAT1 is demonstrated to be involved in acute promyelocytic leukemia (APL), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and also CML (9)(10)(11)(12). However, its role in CML is poorly understood.…”

LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

“…However, NEAT1 has been reported as deregulated in neurodegenerative diseases [ 11 ] and in the majority of tumors [ 2 ] and is known to be a direct target of the transcription factor p53 that, as is common and established knowledge, is defined as the guardian of the genome [ 3 , 4 , 50 , 51 , 52 ]. Based on these considerations, further studies will be important to unravel more precise mechanisms of NEAT1 involvement in genome integrity control and maintenance, which could likely provide a rationale for the development of NEAT1-based therapeutic options in human diseases.…”

“…NEAT1 has been identified and validated as a p53 target by several studies that also pointed out the impairment of DDR efficiency in NEAT1 depleted cells [ 3 , 4 , 50 , 51 , 52 ]. In detail, in 2015 Blume et al reported that the induction of NEAT1 in chronic lymphocytic leukemia (CLL) primary cells could play a role in the DNA damage pathway [ 4 ], demonstrating that, after DNA damage, NEAT1 is induced in the presence of functional p53 but not in CLL carrying p53 mutation, and that its induction is closely related to cell death upon DNA damage [ 4 ].…”

LINC00152 expression in normal and Chronic Lymphocytic Leukemia B cells

“…Conversely, the expression of lincRNA‐p21 is significantly reduced in CLL patients, and low expression of this lncRNA demarcates a more aggressive form of CLL with a poor prognosis 15 . LincRNA‐p21 and the paraspeckle‐enriched lncRNA NEAT1 are involved in the induction of cell death after DNA damage 16 ; however, we recently observed that the expression of NEAT1 is quite heterogeneous in B cells derived from CLL patients irrespectively of cytogenetic groups or clinical outcome 17 …”