Abstract
BackgroundLncRNA NEAT1 has been identified as a tumour driver in many human cancers. However, the underlying mechanism of lncRNA NEAT1 in diffuse large B-cell lymphoma (DLBCL) progression is unclear.MethodsThe expression levels of NEAT1, GLI1 and miR-34b-5p were detected by RT-qPCR and Western blotting in DLBCL tissues and cell lines. MTT and colony formation assays were performed to examine cell proliferation, while annexin-V staining and TUNEL assays were performed to measure cell apoptosis. The effect of NEAT1, GLI1 and miR-34b-5p on cell cycle-associated proteins was evaluated by Western blotting. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were employed to investigate the interaction between NEAT1 and miR-34b-5p or GLI1 and miR-34b-5p. Moreover, chromatin immunoprecipitation (ChIP) was performed to demonstrate the interaction between MYC and NEAT1.ResultsNEAT1 and GLI1 were upregulated while miR-34b-5p was downregulated in DLBCL tissues and cell lines compared to normal controls. Knockdown of NEAT1 or overexpression of miR-34b-5p inhibited cell proliferation but promoted cell apoptosis. Overexpression of NEAT1 reversed GLI1-knockdown induced attenuation of cell proliferation. In other words, NEAT1 acted as a competing endogenous RNA (ceRNA), regulating the miR-34b-5p-GLI1 axis, further affecting the proliferation of DLBCL. Moreover, MYC modulated NEAT1 transcription by directly binding to the NEAT1 promoter.ConclusionWe revealed that MYC-regulated NEAT1 promoted DLBCL proliferation via the miR-34b-5p-GLI1 pathway, which could provide a novel therapeutic target for DLBCL.
Highlights
LncRNA NEAT1 has been identified as a tumour driver in many human cancers
LncRNAs NEAT1 and GLI1 were upregulated while miR‐34b‐5p was downregulated in diffuse large B-cell lymphoma (DLBCL) tissues and cell lines To investigate the role of Long noncoding RNAs (lncRNAs) NEAT and GLI1 in DLBCL, we first measured their expression in MYC-positive DLBCL patients with or without MYC rearrangement and in normal samples by room temperature (RT)-qPCR
These results indicated that MYC rearrangement may affect the prognosis of DLBCL, but the expression of MYC protein is related to the development of DLBCL by other mechanisms
Summary
LncRNA NEAT1 has been identified as a tumour driver in many human cancers. The underly‐ ing mechanism of lncRNA NEAT1 in diffuse large B-cell lymphoma (DLBCL) progression is unclear. Aberrant expression of lncRNA NEAT1 is found in DLBCL. Agarwal et al identified GLI1 as providing insights into the contribution of Hedgehog signaling in the pathobiology of malignant tumours [7]. GLI1 contributes to the cell survival of DLBCL through the expression of AKT in DLBCL and likely in other malignant tumours. Active IKKβ promotes GLI1 expression, leading to the increased cell viability of DLBCL in vivo and in vitro [8]. Sun et al found that GLI1 inhibition repressed cell growth and cell cycle progression and promoted apoptosis as well as autophagy depending on ERK1/2 activity in human chondrosarcoma cells [9]
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