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在子宫内膜癌中,miR-135a通过靶向ASPH发挥肿瘤抑制作用。

miR-135a acts as a tumor suppressor by targeting ASPH in endometrial cancer.

作者信息

Chen Xiaolin, Jin Ping, Tang Huiru, Zhang Lei

机构信息

Department of Gynaecology, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University Shenzhen, P. R. China.

Department of Obstetrics and Gynaecology, Peking University Shenzhen Hospital Shenzhen, P. R. China.

出版信息

Int J Clin Exp Pathol. 2019 Sep 1;12(9):3384-3389. eCollection 2019.

Abstract

Endometrial cancer (EC) ranks as the fourth most commonly diagnosed cancer type in women 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-135a was correlated with tumorigenesis in various cancers. However, its expression and biologic role in EC remained to be determined. This study aimed to clarify whether miR-135a acts as a tumor suppressor in EC by regulating the expression of aspartate-β-hydroxylase (ASPH). Expression of miR-135a was measured by qRT-PCR and the results demonstrated that miR-135a was downregulated in EC cell lines compared to a normal cell line. Cell counting kit-8 (CCK-8) and wound-healing assays demonstrated that overexpression of miR-135a significantly inhibited cell proliferation and migration. Online prediction algorithm and dual luciferase activity reporter assay revealed that ASPH acts as a direct target of miR-135a. ASPH expression was downregulated in EC cell lines when miR-135a was overexpressed. Collectively, our results indicate that miR-135a targets ASPH to inhibit EC cell proliferation and migration, suggesting a tumor suppressive role of miR-135a 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-135a与多种癌症的肿瘤发生相关。然而,其在EC中的表达及生物学作用仍有待确定。本研究旨在通过调节天冬氨酸-β-羟化酶(ASPH)的表达来阐明miR-135a在EC中是否作为肿瘤抑制因子发挥作用。通过qRT-PCR检测miR-135a的表达,结果表明与正常细胞系相比,miR-135a在EC细胞系中表达下调。细胞计数试剂盒-8(CCK-8)和伤口愈合实验表明,miR-135a的过表达显著抑制细胞增殖和迁移。在线预测算法和双荧光素酶活性报告基因检测显示,ASPH是miR-135a的直接靶点。当miR-135a过表达时,EC细胞系中ASPH的表达下调。总体而言,我们的结果表明miR-135a靶向ASPH以抑制EC细胞增殖和迁移,提示miR-135a在EC中具有肿瘤抑制作用。

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