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微小RNA-27a作为一种癌基因,通过靶向泛素特异性蛋白酶46来调控子宫内膜癌的进展。

miR-27a acts as an oncogene to regulate endometrial cancer progression by targeting USP46.

作者信息

Hao Liying, Wang Jiandong

机构信息

Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing, P. R. China.

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing, P. R. China.

出版信息

Int J Clin Exp Pathol. 2021 Jun 15;14(6):720-725. eCollection 2021.

PMID:34239673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8255193/
Abstract

Endometrial cancer (EC) ranks as the fourth most common diagnosed cancer type in females worldwide. MicroRNAs (miRNAs) are important regulators with crucial roles in regulating diverse biologic processes, including tumor initiation and progression. Previous studies have demonstrated that miR-27a was correlated with the tumorigenesis of various cancers. However, its expression and biologic role in EC remain to be determined. This study aimed to clarify whether miR-27a acts as an oncogene in endometrial cancer (EC) by downregulating ubiquitin specific peptidase 46 (USP46). Expression of miR-27a was measured by qRT-PCR, and the results demonstrated that miR-27a was upregulated in EC cell lines compared to normal cell lines. Cell counting kit-8 (CCK-8) and wound-healing assays demonstrated that overexpression of miR-27a significantly promoted cell proliferation and migration. Online prediction algorithm and dual luciferase activity reporter assay revealed that USP46 acts as a direct target of miR-27a. USP46 expression was downregulated in EC cell lines during miR-27a overexpression. Collectively, our results indicated that miR-27a targets USP46 to promote EC cell proliferation and migration, suggesting an oncogene role of miR-27a in EC.

摘要

子宫内膜癌(EC)是全球女性中第四大最常被诊断出的癌症类型。微小RNA(miRNA)是重要的调节因子,在调控包括肿瘤发生和进展在内的多种生物学过程中发挥关键作用。先前的研究表明,miR-27a与多种癌症的肿瘤发生相关。然而,其在子宫内膜癌中的表达及生物学作用仍有待确定。本研究旨在通过下调泛素特异性肽酶46(USP46)来阐明miR-27a在子宫内膜癌(EC)中是否作为一种癌基因发挥作用。通过qRT-PCR检测miR-27a的表达,结果表明与正常细胞系相比,miR-27a在EC细胞系中上调。细胞计数试剂盒-8(CCK-8)和伤口愈合试验表明,miR-27a的过表达显著促进细胞增殖和迁移。在线预测算法和双荧光素酶活性报告基因试验显示,USP46是miR-27a的直接靶点。在miR-27a过表达期间,EC细胞系中USP46的表达下调。总体而言,我们的结果表明,miR-27a靶向USP46以促进EC细胞增殖和迁移,提示miR-27a在EC中具有癌基因作用。

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本文引用的文献

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Cancer Biomark. 2019;24(1):31-42. doi: 10.3233/CBM-181229.
2
The novel anti-androgen candidate galeterone targets deubiquitinating enzymes, USP12 and USP46, to control prostate cancer growth and survival.新型抗雄激素候选药物加列酮靶向去泛素化酶USP12和USP46,以控制前列腺癌的生长和存活。
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miR‑215 promotes epithelial to mesenchymal transition and proliferation by regulating LEFTY2 in endometrial cancer.miR-215 通过调节子宫内膜癌细胞中的 LEFTY2 促进上皮间质转化和增殖。
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Tumor-suppressor role of miR-139-5p in endometrial cancer.miR-139-5p在子宫内膜癌中的肿瘤抑制作用。
Cancer Cell Int. 2018 Apr 2;18:51. doi: 10.1186/s12935-018-0545-8. eCollection 2018.
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miR-148b Functions as a Tumor Suppressor by Targeting Endoplasmic Reticulum Metallo Protease 1 in Human Endometrial Cancer Cells.miR-148b 通过靶向人子宫内膜癌细胞中的内质网金属蛋白酶 1 发挥肿瘤抑制作用。
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PLoS One. 2017 Oct 24;12(10):e0186718. doi: 10.1371/journal.pone.0186718. eCollection 2017.
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