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长链非编码 RNA NEAT1 通过靶向 miR-485-5p/ABCB8 促进多发性骨髓瘤恶性转化。

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

机构信息

Department of Hematology-oncology, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan, People's Republic of China.

Zhumadian Central Hospital, Zhumadian, Henan, People's Republic of China.

出版信息

Hematology. 2024 Dec;29(1):2422153. doi: 10.1080/16078454.2024.2422153. Epub 2024 Oct 30.

DOI:10.1080/16078454.2024.2422153
PMID:39475764
Abstract

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.

摘要

多发性骨髓瘤(MM)是全世界第二常见的血液系统恶性肿瘤。长链非编码 RNA(lncRNA)核富集常染色体转录本 1(NEAT1)已被报道在多种人类恶性肿瘤如 MM 的发生和发展中发挥重要作用。然而,NEAT1 在 MM 进展中的功能作用和分子机制仍需要更多的研究来确定 MM 的潜在靶点。在本研究中,我们重点研究了 NEAT1 在 MM 中的临床和生物学意义。我们证明了 NEAT1 在 MM 组织和细胞系中上调。NEAT1 沉默显著抑制了体外细胞增殖并促进了细胞凋亡。我们阐明了 miR-485-5p 是 NEAT1 的直接靶标,下调 NEAT1 对 MM 细胞的作用部分被 miR-485-5p 反义寡核苷酸(ASO-miR-485-5p)逆转。进一步的研究表明 ABCB8 直接与 miR-485-5p 相互作用。同样,体内实验证实下调 NEAT1 抑制了肿瘤生长和 ABCB8 表达。综上所述,我们的研究结果首次表明,NEAT1/miR-485-5p/ABCB8 轴可能是 MM 发生和发展的关键途径,它们可能为靶向治疗提供新的途径。

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