NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2.
NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2.
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DOI：
10.2147/ott.s142446
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发表时间：
2017
影响因子：
4
通讯作者：
Peng E
中科院分区：
文献类型：
--
作者：
Ding N;Wu H;Tao T;Peng E
核富集丰富转录物 1 (NEAT1) 已被证明可在许多癌症中充当肿瘤抑制剂。然而，NEAT1 在卵巢癌 (OC) 发展中的作用尚未得到详细阐述。因此，本研究的目的是研究 NEAT1 在 OC 中的表达和功能。通过实时定量聚合酶链式反应测定 OC 细胞系中 NEAT1 的表达水平。采用MTT法、caspase-3活性测定和流式细胞术分析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。使用荧光素酶报告基因测定来确认 OC 细胞中 NEAT1、BCL2 和 miR-34a-5p 的相互作用。 NEAT1 在 OC 细胞系中显着上调。 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NEAT1敲低则具有相反的作用。此外，NEAT1 被证明可直接与 miR-34a-5p 相互作用，并通过负向调节 miR-34a-5p 发挥其在 OC 中的致癌作用。此外，miR-34a-5p可以直接靶向BCL2并抑制其表达。 miR-34a-5p 过表达抑制 OC 细胞增殖并通过靶向 BCL2 触发细胞凋亡。此外，NEAT1 敲低抑制了 BCL2 表达，而抗 miR-34a-5p 则显着减弱了 si-NEAT1 对 BCL2 表达的抑制作用。 NEAT1通过miR-34a-5p/BCL2调节OC细胞的增殖和凋亡，为OC患者的治疗提供了潜在的治疗方法。
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. 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. 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. NEAT1 regulated proliferation and apoptosis of OC cells by miR-34a-5p/BCL2, providing a potential therapeutic approach for the treatment of OC patients.