Long non-coding RNA NEAT1 promotes multiple myeloma malignant transformation via targeting miR-485-5p/ABCB8

Multiple myeloma (MM) is the second most common hematological cancer all over the world. Long non-coding RNA (lncRNA) nuclear-enriched autosomal transcript-1 (NEAT1) have been reported to play important roles in the development and progression of multiple human malignancies like MM. However, the functional role and molecular mechanism of NEAT1 in MM progression still needs more support to identify potential targets of MM. In the present study, we focused on the clinical and biological significance of NEAT1 in MM. We demonstrated that NEAT1 was up-regulated in MM tissues and cell line. NEAT1 silencing significantly inhibited cell proliferation and promoted cell apoptosis in vitro. And we illustrated that miR-485-5p was a direct target of NEAT1 and the effect of down-regulated NEAT1 on MM cells was partially reversed by the miR-485-5p antisense oligonucleotide (ASO-miR-485-5p). Further investigation revealed that ABCB8 directly interacted with miR-485-5p. Similarly, in vivo experiments confirmed that down-regulated NEAT1 inhibited tumor growth and ABCB8 expression. Taken together, our results demonstrate for the first time that NEAT1/miR-485-5p/ABCB8 axis may be a key pathway for the development and progression of MM, and they may provide a novel avenue for targeted therapy. The effects of the comprehensive NEAT1–miRNA regulatory network in MM needs more support. Our results demonstrate for the first time that NEAT1/miR-485-5p/ABCB8 axis may be a key pathway for the development and progression of MM, which may provide a novel avenue for targeted therapy.

多发性骨髓瘤（Multiple Myeloma, MM）是全球范围内第二高发的血液系统恶性肿瘤。已有研究显示，长链非编码RNA（long non-coding RNA, lncRNA）核富集常染色体转录本1（nuclear-enriched autosomal transcript-1, NEAT1）在多发性骨髓瘤等多种人类恶性肿瘤的发生与进展过程中发挥关键调控作用。然而，NEAT1在多发性骨髓瘤进展中的功能角色及分子机制，仍需更多研究以验证其作为多发性骨髓瘤潜在治疗靶点的潜力。
本研究聚焦于NEAT1在多发性骨髓瘤中的临床与生物学意义。研究结果证实，NEAT1在多发性骨髓瘤组织及细胞系中呈高表达状态。沉默NEAT1可显著抑制多发性骨髓瘤细胞的体外增殖，并促进其凋亡。本研究进一步阐明，miR-485-5p是NEAT1的直接靶标，且下调NEAT1对多发性骨髓瘤细胞产生的生物学效应，可被miR-485-5p反义寡核苷酸（antisense oligonucleotide, ASO-miR-485-5p）部分逆转。后续机制研究发现，ABCB8可与miR-485-5p直接相互作用。体内实验同样证实，下调NEAT1可抑制肿瘤生长并降低ABCB8的表达水平。
综上，本研究首次证实NEAT1/miR-485-5p/ABCB8调控轴可能是多发性骨髓瘤发生发展的关键通路，可为该疾病的靶向治疗提供全新思路。目前，综合性NEAT1-miRNA调控网络在多发性骨髓瘤中的作用仍需更多研究佐证。本研究首次证实NEAT1/miR-485-5p/ABCB8调控轴可作为多发性骨髓瘤发生发展的关键通路，为其靶向治疗开辟全新途径。