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miR-574-3p 通过抑制 MMP3 表达在卵巢癌中发挥肿瘤抑制作用。

MiR-574-3p exerts as a tumor suppressor in ovarian cancer through inhibiting MMP3 expression.

机构信息

Department of Immunology, Medical College of Soochow University, Suzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):6839-6848. doi: 10.26355/eurrev_201908_18723.

DOI:10.26355/eurrev_201908_18723
PMID:31486483
Abstract

OBJECTIVE

The mortality rate of ovarian cancer (OC) has always been the highest among all female reproductive system malignant tumors. Currently, miRNAs have been verified to participate in the tumorigenesis and prognosis of OC. However, the expression and function of miR-574-3p in OC have not been fully elucidated.

PATIENTS AND METHODS

The expression level of miR-574-3p in OC tissues and cells was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). By transfection of miR-574-3p mimics or inhibitor, the expression of miR-574-3p in SW626 or A2780 cells was up-regulated or down-regulated, respectively. Cell counting kit-8 (CCK-8) and colony formation assays were used to measure the proliferation of transfected OC cells. Meanwhile, the transwell assay was applied to detect the migration and invasion abilities of OC cells. Furthermore, dual-luciferase reporter gene analysis and Western blot were utilized to explore the underlying downstream molecules for miR-574-3p in OC.

RESULTS

MiR-574-3p was lowly expressed in OC tissue samples when compared with para-tumor tissues. Meanwhile, the expression of miR-574-3p in OC-derived cells was significantly lower than normal control HOSE cells. The overexpression of miR-574-3p markedly reduced the proliferation, invasion, and migration of SW626 cells. However, the inhibition of miR-574-3p remarkably accelerated the growth and metastasis of A2780 cells. MMP3 was verified as a direct target for miR-574-3p in OC. In addition, miR-574-3p could reduce the protein expression of MMP3 by binding to its 3'-untranslated region (3'-UTR).

CONCLUSIONS

MiR-574-3p functioned as a tumor suppressor in OC, which might be served as a potential target for the diagnosis and therapy for OC.

摘要

目的

卵巢癌(OC)的死亡率一直是女性生殖系统恶性肿瘤中最高的。目前,miRNA 已被证实参与 OC 的发生和预后。然而,miR-574-3p 在 OC 中的表达和功能尚未完全阐明。

患者与方法

采用实时定量聚合酶链反应(qRT-PCR)检测 OC 组织和细胞中 miR-574-3p 的表达水平。通过转染 miR-574-3p 模拟物或抑制剂,分别上调或下调 SW626 或 A2780 细胞中 miR-574-3p 的表达。细胞计数试剂盒-8(CCK-8)和集落形成实验用于测量转染 OC 细胞的增殖。同时,Transwell 实验用于检测 OC 细胞的迁移和侵袭能力。此外,双荧光素酶报告基因分析和 Western blot 用于探索 OC 中 miR-574-3p 的潜在下游分子。

结果

与配对肿瘤组织相比,OC 组织样本中 miR-574-3p 表达水平较低。同时,OC 来源细胞中的 miR-574-3p 表达明显低于正常对照 HOSE 细胞。miR-574-3p 的过表达显著降低了 SW626 细胞的增殖、侵袭和迁移。然而,miR-574-3p 的抑制显著加速了 A2780 细胞的生长和转移。MMP3 被验证为 OC 中 miR-574-3p 的直接靶标。此外,miR-574-3p 通过与其 3'-非翻译区(3'-UTR)结合来降低 MMP3 的蛋白表达。

结论

miR-574-3p 在 OC 中作为肿瘤抑制因子发挥作用,可能作为 OC 诊断和治疗的潜在靶点。

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