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NEAT1 通过激活 PI3K/AKT 通路促进多发性骨髓瘤细胞增殖。

NEAT1 promotes cell proliferation in multiple myeloma by activating PI3K/AKT pathway.

机构信息

Department of Hematology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Oct;22(19):6403-6411. doi: 10.26355/eurrev_201810_16053.

DOI:10.26355/eurrev_201810_16053
PMID:30338809
Abstract

OBJECTIVE

The role of long-chain non-coding NEAT1 (Nuclear enriched abundant transcript1) in multiple myeloma (MM) and its underlying mechanisms were investigated.

PATIENTS AND METHODS

The expression of NEAT1 and SOX13 was detected in CD138+ positive cells collected from MM and healthy subjects. Meanwhile, the relationship between NEAT1 level and the prognosis as well as clinical staging was analyzed. Virus transfection method was used to change the expression of NEAT1 and SOX13 in tumor cells, and then the effect of NEAT1 on cell proliferation, apoptosis and cell cycle was examined. The influence of NEAT1 on the regulation of SOX13 was explored through recovery experiments and Western blot. In addition, the regulation effect of NEAT1 on tumor formation was explored in vivo.

RESULTS

NEAT1 and SOX13 were highly expressed in MM patients and MM cell lines, and the patient survival rate and platelet count were significantly decreased in the highly expressed NEAT1 group. Low expression of NEAT1 could inhibit the PI3K/AKT pathway to suppress cell proliferation, promote apoptosis, and inhibit cell cycle. Overexpression of SOX13 was able to partially restore the inhibitory effect of NEAT1 on cell proliferation. Meanwhile, it was found that low expression of NEAT1 significantly inhibited tumor formation in vivo.

CONCLUSIONS

Highly expressed NEAT1 promoted cell proliferation through activation of PI3K/AKT pathway, thus participating in the development of MM.

摘要

目的

研究长链非编码 NEAT1(核丰富丰富转录物 1)在多发性骨髓瘤(MM)中的作用及其潜在机制。

患者和方法

从 MM 患者和健康受试者的 CD138+阳性细胞中检测 NEAT1 和 SOX13 的表达。同时,分析 NEAT1 水平与预后和临床分期的关系。采用病毒转染方法改变肿瘤细胞中 NEAT1 和 SOX13 的表达,然后检测 NEAT1 对细胞增殖、凋亡和细胞周期的影响。通过恢复实验和 Western blot 探索 NEAT1 对 SOX13 调节的影响。此外,还在体内探索了 NEAT1 对肿瘤形成的调节作用。

结果

NEAT1 和 SOX13 在 MM 患者和 MM 细胞系中高表达,高表达 NEAT1 组患者的生存率和血小板计数明显降低。低表达 NEAT1 可抑制 PI3K/AKT 通路,抑制细胞增殖,促进细胞凋亡,抑制细胞周期。SOX13 的过表达能够部分恢复 NEAT1 对细胞增殖的抑制作用。同时,发现低表达 NEAT1 可显著抑制体内肿瘤形成。

结论

高表达的 NEAT1 通过激活 PI3K/AKT 通路促进细胞增殖,从而参与 MM 的发生发展。

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