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miRNA-8073 通过靶向 ZnT1 抑制卵巢癌细胞的恶性进展。

MiRNA-8073 targets ZnT1 to inhibit malignant progression of ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Wuhan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6062-6069. doi: 10.26355/eurrev_201907_18419.

DOI:10.26355/eurrev_201907_18419
PMID:31364107
Abstract

OBJECTIVE

The purpose of this study was to investigate the effect of microRNA-8073 on the malignant progression of ovarian cancer (OC) and whether the underlying mechanism is through the regulation of ZnT1 expression.

PATIENTS AND METHODS

Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-8073 in 50 tumor tissues and adjacent tissues of OC patients, and the relationship between microRNA-8073 expression and clinical indicators of OC was analyzed. Negative control group (NC) and microRNA-8073 overexpression group (microRNA-8073 mimics) were set in OC cell lines, and the transfection efficiency was further verified by qRT-PCR. In OC cell lines including SKOV3 and OVCAR3, the effects of microRNA-8073 on cell proliferation and apoptosis were analyzed by cell counting kit-8 (CCK-8), cell clone formation assay, and flow cytometry. Finally, the regulatory mechanism of microRNA-8073 on the downstream gene ZnT1 was explored by a recovery experiment.

RESULTS

QRT-PCR results revealed that microRNA-8073 expression in cancer tissue specimens of OC patients was significantly lower than that in corresponding normal tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-8073, NC group had low expression of microRNA-8073 and had a higher pathological stage and lower overall survival rate. In the OC cell lines including SKOV3 and OVCAR3, compared with the NC group, the cell proliferation ability of the microRNA-8073 mimics group was significantly decreased, while the apoptotic ability was significantly increased. Also, ZnT1 had high expression in OC cell lines and tissues and was confirmed negatively correlated with microRNA-8073 level. Meanwhile, the recovery experiment revealed that overexpression of ZnT1 can counteract the effect of microRNA-8073 mimics on OC cell proliferation and apoptosis so as to affect the malignant progression of OC.

CONCLUSIONS

We demonstrated that microRNA-8073 was significantly associated with the pathological stage and poor prognosis of OC. In addition, microRNA-8073 might inhibit malignant progression of OC by regulating ZnT1 expression.

摘要

目的

本研究旨在探讨 microRNA-8073 对卵巢癌(OC)恶性进展的影响,以及其潜在机制是否通过调节 ZnT1 表达。

方法

采用实时定量聚合酶链反应(qRT-PCR)检测 50 例 OC 患者肿瘤组织和癌旁组织中 microRNA-8073 的表达,分析 microRNA-8073 表达与 OC 临床指标的关系。在 OC 细胞系中设置阴性对照组(NC)和 microRNA-8073 过表达组(microRNA-8073 模拟物),并通过 qRT-PCR 进一步验证转染效率。在 OC 细胞系 SKOV3 和 OVCAR3 中,通过细胞计数试剂盒-8(CCK-8)、细胞克隆形成实验和流式细胞术分析 microRNA-8073 对细胞增殖和凋亡的影响。最后,通过恢复实验探讨 microRNA-8073 对下游基因 ZnT1 的调控机制。

结果

qRT-PCR 结果显示,OC 患者癌组织标本中 microRNA-8073 的表达明显低于相应的正常组织,差异具有统计学意义。与 microRNA-8073 高表达的患者相比,NC 组 microRNA-8073 表达较低,且病理分期较高,总生存率较低。在 OC 细胞系 SKOV3 和 OVCAR3 中,与 NC 组相比,microRNA-8073 模拟物组的细胞增殖能力明显降低,而凋亡能力明显增强。此外,ZnT1 在 OC 细胞系和组织中高表达,与 microRNA-8073 水平呈负相关。同时,恢复实验表明,过表达 ZnT1 可拮抗 microRNA-8073 模拟物对 OC 细胞增殖和凋亡的影响,从而影响 OC 的恶性进展。

结论

我们证实,microRNA-8073 与 OC 的病理分期和预后不良显著相关。此外,microRNA-8073 可能通过调节 ZnT1 表达抑制 OC 的恶性进展。

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