ABSTRACT: 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 (?2-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, ?2-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.