Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma

Taìana, Elisa; Favasuli, Vanessa; Ronchetti, Domenica; Todoerti, Katia; Pelizzoni, F.; Manzoni, Martina; Barbieri, Marzia; Fabris, Sonia; Silvestris, I.; Cantafio, Maria Eugenia Gallo; Platonova, N.; Zuccalà, Valeria; Maltese, Lorenza; Soncini, Debora; Ruberti, Samantha; Cea, Michele; Chiaramonte, R.; Amodio, Nicola; Tassone, Pierfrancesco; Agnelli, Luca; Neri, Antonino

doi:10.1038/s41375-019-0542-5

Cited by 90 publications

(77 citation statements)

References 27 publications

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“…We enrolled MM patients and healthy donors, whose BM samples were collected for detecting lncRNA NEAT1 expression, and found that lncRNA NEAT1 was upregulated in MM patients compared with healthy donors and present excellent value in distinguishing MM patients from healthy donors. This was consistent with the previous studies, suggesting that lncRNA NEAT1 was an oncogenic gene in MM pathology and has potential to be a biomarker for predicting MM risk 12,22,23 …”

Section: Discussionsupporting

confidence: 92%

Long non‐coding RNA NEAT1 serves as a novel biomarker for treatment response and survival profiles via microRNA‐125a in multiple myeloma

Peng

Chen

et al. 2020

Clinical Laboratory Analysis

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Background The present study aimed to explore the association of long non‐coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) with multiple myeloma (MM) risk and further investigate its correlation with clinical features, treatment response, survival profiles, and its interaction with microRNA‐125a (miR‐125a) in MM patients. Methods Totally, 114 de novo symptomatic MM patients and 30 healthy donors (as controls) were recruited. Their bone marrow samples were collected before treatment (MM patients) and at enrollment (healthy donors), respectively. Subsequently, plasma cells were isolated from bone marrow for detection of lncRNA NEAT1 and miR‐125a expression via reverse transcription quantitative polymerase chain reaction. Results lncRNA NEAT1 was upregulated in MM patients compared with healthy donors and presented with excellent value in distinguishing MM patients from healthy donors. In MM patients, lncRNA NEAT1 positively associated with International Staging System (ISS) stage, beta‐2 microglobulin (β2‐MG), and lactate dehydrogenase (LDH), but not correlated with core cytogenetics and other clinical features. Furthermore, lncRNA NEAT1 negatively associated with complete remission (CR), overall remission rate (ORR), progression‐free survival (PFS), and overall survival (OS). Moreover, lncRNA NEAT1 negatively associated with miR‐125a in MM patients. MiR‐125a was downregulated in MM patients compared with healthy donors, and it negatively associated with ISS stage, β2‐MG, and LDH, but positively correlated with CR, ORR, PFS, and OS in MM patients. Conclusion lncRNA NEAT1 might interact with miR‐125a, and serves as a novel biomarker for treatment response and survival profiles in MM, indicating its clinical value for MM management.

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Section: Discussionsupporting

confidence: 92%

Long non‐coding RNA NEAT1 serves as a novel biomarker for treatment response and survival profiles via microRNA‐125a in multiple myeloma

Peng

Chen

et al. 2020

Clinical Laboratory Analysis

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“…Data regarding the impact of NEAT1 and PSs in carcinogenesis and the underlying mechanisms of their deregulation are progressively emerging [ 2 ]. In particular, recent experimental data in different types of tumors have suggested the involvement of NEAT1 and/or PSs in the context of DNA damage repair (DDR) systems [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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

Taìana

Ronchetti

Todoerti

et al. 2020

ncRNA

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Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases.

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“…Generally, circulating miR‐193a‐5p expression is decreased in human cancers, and its downregulation correlates with advanced progression (Gougelet et al ., ; Zhang et al ., ). Intriguing results from two recent studies support our data with a reliable molecular mechanism showing that downregulated long non‐coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) linked to higher circulating miR‐193a‐5p expression levels (Wu & Wang, ) is associated with favourable sensitizing effects of commonly used chemotherapeutic agents including bortezomib, carfilzomib and melphalan (Taiana et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Predictive impact of circulating microRNA‐193a‐5p on early relapse after autologous stem cell transplantation in patients with multiple myeloma

et al. 2020

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We explored prognostic roles of circulating microRNAs (miRs) in multiple myeloma (MM) treated with autologous stem cell transplantation (ASCT) following induction chemotherapy. In part I of the study (n = 40), we identified a decreasing dynamics of circulating miR-193a-5p expression from diagnosis to pre-ASCT. In patients who experienced early relapse within one year post ASCT (n = 9) these patterns were distinctive compared to those without early relapse in a 1:2 matched cohort (n = 18). In part II (n = 90), multivariate analyses showed that the International Staging System score and miR-193a-5p expression before ASCT were independent prognostic factors. Conclusively, expression of circulating miR-193a-5p before ASCT could be a prognostic biomarker for transplant-eligible MM.

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Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma

Cited by 90 publications

References 27 publications

Long non‐coding RNA NEAT1 serves as a novel biomarker for treatment response and survival profiles via microRNA‐125a in multiple myeloma

Long non‐coding RNA NEAT1 serves as a novel biomarker for treatment response and survival profiles via microRNA‐125a in multiple myeloma

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

Predictive impact of circulating microRNA‐193a‐5p on early relapse after autologous stem cell transplantation in patients with multiple myeloma

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