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

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 (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.

lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis

“…In this study, lncRNA NEAT1, as mentioned before, is also involved in the pathological development of diseases. A study found that lncRNA NEAT1 could be used as a biomarker of multiple myeloma, and myeloma cells could inhibit the differentiation of BMSCs into osteoblasts [ 27 ]. Overexpression of NEAT1 has also been shown to promote osteoclast formation [ 12 ].…”

The Role of lncRNAs in the Pathobiology and Clinical Behavior of Multiple Myeloma

“…These results highlight the cell- and tissue- specificity of lncRNAs, showing that their deregulation—and thus, their potential function—needs to be addressed in each tumor. For example, MALAT1 (one of the most widely studied lncRNAs [ 103 ]) and NEAT1 are able to bind or interfere with different molecules and pathways depending on the tissue or disease ( Table 1 ) [ 77 , 106 ]. MALAT1 acts as an miRNA sponge binding to miR-1271-5p ( Figure 1 ), miR-181a-5p and miR-509-5p in MM, to miR-195 in HCC or to miR-206 and miR-363-3p in gallbladder cancer [ 63 , 65 , 66 , 67 , 68 ].…”

“…MALAT1 acts as an miRNA sponge binding to miR-1271-5p ( Figure 1 ), miR-181a-5p and miR-509-5p in MM, to miR-195 in HCC or to miR-206 and miR-363-3p in gallbladder cancer [ 63 , 65 , 66 , 67 , 68 ]. In the case of NEAT1 , it binds to miR-125a in MM and to miR-193a-3p in lung adenocarcinoma, among others [ 77 , 106 ]. Usually, the expression of lncRNAs and miRNAs is negatively correlated.…”

“…Usually, the expression of lncRNAs and miRNAs is negatively correlated. Therefore, overexpression of one lncRNA could trigger the downregulation of miRNAs, whereas downregulation of one lncRNA could promote the overexpression of different miRNAs [ 33 , 77 ]. Likewise, there are other examples of lncRNAs which act as miRNA sponges in MM ( Table 1 ).…”

“…The overexpression of the cytoplasmic circular lncRNA Circ_0000190, MEG3 and PRAL has been associated with better PFS and OS, and high expression levels of SMILO (specific myeloma intergenic long non-coding RNA) with better OS in MM patients [ 13 , 36 , 72 , 86 , 87 ]. By contrast, high expression levels of lnc-TCF7 , MALAT1 , MIAT , NEAT1 and PDLIM1P4 have been associated with worse PFS and OS in MM patients [ 13 , 61 , 63 , 70 , 75 , 76 , 77 , 80 ], the overexpression of CRNDE , LINC00152 , LINC00461 , LINC01234 , lnc-ANGPTL1-3 , PDIA3P and UCA1 with worse OS, and the overexpression of ENSG00000254343 , H19 and NR_046683 (also known as ST3GAL6-AS1 , ST3GAL6 antisense RNA 1) with worse PFS in MM patients [ 13 , 40 , 46 , 56 , 85 , 93 , 95 ]. In addition, high expression levels of LUCAT1 were associated with worse five-year survival rates [ 62 ], and MM patients with the lncRNA BM742401 methylated showed worse OS than those patients with unmethylated BM742401 [ 35 ].…”