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微小RNA-651-3p通过靶向锌指蛋白703并经由丝裂原活化蛋白激酶/细胞外信号调节激酶(MEK/ERK)信号通路调控卵巢癌细胞的上皮-间质转化。

miRNA-651-3p regulates EMT in ovarian cancer cells by targeting ZNF703 and via the MEK/ERK pathway.

作者信息

Wang Shuang, Wang Caixia, Liu Ouxuan, Hu Yuexin, Li Xiao, Lin Bei

机构信息

Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical University, Liaoning, China; Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Liaoning, China.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

出版信息

Biochem Biophys Res Commun. 2022 Sep 3;619:76-83. doi: 10.1016/j.bbrc.2022.06.005. Epub 2022 Jun 16.

Abstract

miRNAs are non-coding single-stranded RNA molecules with many functions. Several miRNAs have been found to be dysregulated in ovarian cancer; however, the role of miR-651-3p in ovarian cancer remains unknown. Here, the expression level of miR-651-3p in ovarian tissue samples was determined via qRT-PCR, and then miR-651-3p was overexpressed and downregulated to study the functional changes in ovarian cancer cells. Based on previous research and database predictions, we analyzed the binding and regulatory effects of miR-651-3p on zinc finger protein 703 (ZNF703). We additionally evaluated the effect of miR-651-3p on epithelial-mesenchymal transition (EMT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways in ovarian cancer cells. We found that miR-651-3p was downregulated in ovarian cancer tissues. miR-651-3p expression was associated with inhibited proliferation, invasion, and migration of ovarian cancer cells and promoted cell cycle arrest. Additionally, miR-651-3p was found to target ZNF703 and affect EMT in ovarian cancer by activating the MEK/ERK signaling pathway. MiR-651-3p was downregulated in ovarian cancer, and suppressed the malignant biological behavior of ovarian cancer by inhibiting ZNF703 and the MEK/ERK pathway. Our findings on miR-651-3p provided new insights for the diagnosis and treatment of ovarian cancer.

摘要

微小RNA(miRNA)是具有多种功能的非编码单链RNA分子。已发现几种miRNA在卵巢癌中表达失调;然而,miR-651-3p在卵巢癌中的作用仍不清楚。在此,通过qRT-PCR测定卵巢组织样本中miR-651-3p的表达水平,然后使miR-651-3p过表达和下调,以研究卵巢癌细胞的功能变化。基于先前的研究和数据库预测,我们分析了miR-651-3p对锌指蛋白703(ZNF703)的结合和调控作用。我们还评估了miR-651-3p对卵巢癌细胞上皮-间质转化(EMT)和丝裂原活化蛋白激酶激酶(MEK)/细胞外信号调节激酶(ERK)通路的影响。我们发现miR-651-3p在卵巢癌组织中表达下调。miR-651-3p的表达与卵巢癌细胞增殖、侵袭和迁移的抑制以及细胞周期停滞的促进有关。此外,发现miR-651-3p靶向ZNF703,并通过激活MEK/ERK信号通路影响卵巢癌中的EMT。miR-651-3p在卵巢癌中表达下调,并通过抑制ZNF703和MEK/ERK通路抑制卵巢癌的恶性生物学行为。我们对miR-651-3p的研究结果为卵巢癌的诊断和治疗提供了新的见解。

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