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NEAT1通过miR-34a-5p/BCL2调控卵巢癌细胞的增殖和凋亡。

NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2.

作者信息

Ding Nan, Wu Haiying, Tao Tao, Peng Erxuan

机构信息

Department of Obstetrics and Gynecology, Henan Provincial People's Hospital.

Department of Obstetrics and Gynecology, Henan Provincial Tumor Hospital, Zhengzhou, China.

出版信息

Onco Targets Ther. 2017 Oct 6;10:4905-4915. doi: 10.2147/OTT.S142446. eCollection 2017.

Abstract

BACKGROUND

Nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to act as a tumor inhibitor in many cancers. However, the role of NEAT1 in the development of ovarian cancer (OC) remains far from being elaborated. Hence, the aim of this study is to investigate the expression and function of NEAT1 in OC.

MATERIALS AND METHODS

The expression level of NEAT1 was determined by quantitative real-time polymerase chain reaction in OC cell lines. MTT assay, caspase-3 activity assay, and flow cytometry analysis were conducted to investigate the effects of NEAT1, miR-34a-5p, or B-cell lymphoma-2 (BCL2) on OC cell proliferation and apoptosis. Luciferase reporter assay was used to confirm the interaction of NEAT1, BCL2, and miR-34a-5p in OC cells.

RESULTS

NEAT1 was significantly upregulated in OC cell lines. NEAT1 overexpression promoted proliferation by increasing the proportion of cells in S phase and suppressed apoptosis of OC cells, while knockdown of NEAT1 had the opposite effect. In addition, NEAT1 was demonstrated to directly interact with miR-34a-5p and exert its oncogenic role in OC by negatively regulating miR-34a-5p. Moreover, miR-34a-5p could directly target BCL2 and suppressed its expression. miR-34a-5p overexpression suppressed OC cell proliferation and triggered apoptosis by targeting BCL2. Furthermore, NEAT1 knockdown suppressed BCL2 expression, while anti-miR-34a-5p dramatically abated the inhibitory effect of si-NEAT1 on BCL2 expression.

CONCLUSION

NEAT1 regulated proliferation and apoptosis of OC cells by miR-34a-5p/BCL2, providing a potential therapeutic approach for the treatment of OC patients.

摘要

背景

核富集丰富转录本1(NEAT1)已被证明在许多癌症中作为肿瘤抑制因子发挥作用。然而,NEAT1在卵巢癌(OC)发生发展中的作用仍远未阐明。因此,本研究旨在探讨NEAT1在OC中的表达及功能。

材料与方法

通过定量实时聚合酶链反应检测OC细胞系中NEAT1的表达水平。采用MTT法、半胱天冬酶-3活性测定法和流式细胞术分析,研究NEAT1、miR-34a-5p或B细胞淋巴瘤-2(BCL2)对OC细胞增殖和凋亡的影响。采用荧光素酶报告基因测定法,证实OC细胞中NEAT1、BCL2和miR-34a-5p之间的相互作用。

结果

NEAT1在OC细胞系中显著上调。NEAT1过表达通过增加S期细胞比例促进增殖,并抑制OC细胞凋亡,而敲低NEAT1则产生相反的效果。此外,NEAT1被证明直接与miR-34a-5p相互作用,并通过负调控miR-34a-5p在OC中发挥致癌作用。此外,miR-34a-5p可直接靶向BCL2并抑制其表达。miR-34a-5p过表达通过靶向BCL2抑制OC细胞增殖并引发凋亡。此外,敲低NEAT1可抑制BCL2表达,而抗miR-34a-5p可显著减弱si-NEAT1对BCL2表达的抑制作用。

结论

NEAT1通过miR-34a-5p/BCL2调节OC细胞的增殖和凋亡,为OC患者的治疗提供了一种潜在的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80f/5640398/a034472564f5/ott-10-4905Fig1.jpg

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