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微小RNA-19a-3p通过下调UBAP2L抑制非小细胞肺癌的细胞增殖和侵袭。

MicroRNA-19a-3p inhibits the cellular proliferation and invasion of non-small cell lung cancer by downregulating UBAP2L.

作者信息

Pan Yuejiang, Jin Ke, Xie Xuan, Wang Kexi, Zhang Huizhong

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.

出版信息

Exp Ther Med. 2020 Sep;20(3):2252-2261. doi: 10.3892/etm.2020.8926. Epub 2020 Jun 24.

Abstract

MicroRNAs (miRNAs) are increasingly recognized as important regulators of non-small cell lung cancer (NSCLC) progression by directly regulating their target genes. The aim of the present study was to assess the biological role of miR-19a-3p in NSCLC. It was revealed that miR-19a-3p expression was significantly downregulated in human NSCLC tissues and cell lines compared with normal tissues and lung epithelial cells. In addition, a lower miR-19a-3p expression was significantly associated with Tumor Node Metastasis stage and lymph node metastasis. Furthermore, the upregulation of miR-19a-3p in NSCLC cell lines significantly inhibited cell proliferation, migration and invasion, as determined using an MTT, colony formation, wound healing and transwell Matrigel invasion assays, respectively. A luciferase reporter assay and western blotting determined that ubiquitin associated protein 2 like (UBAP2L) was a direct target of miR-19a-3p and could be inhibited through the upregulation of miR-19a-3p in NSCLC. In addition, UBAP2L silencing induced similar effects to those observed following miR-19a-3p overexpression. The overexpression of UBAP2L partially reversed the effects of miR-19a-3p on NSCLC cell lines. Collectively, these data indicated that miR-19a-3p may serve as a tumor suppressor partly through the regulation of UBAP2L expression in NSCLC and that the targeting of miR-19a-3p may be a novel method for NSCLC treatment.

摘要

微小RNA(miRNA)通过直接调控其靶基因,日益被认为是非小细胞肺癌(NSCLC)进展的重要调节因子。本研究旨在评估miR-19a-3p在NSCLC中的生物学作用。结果显示,与正常组织和肺上皮细胞相比,miR-19a-3p在人NSCLC组织和细胞系中的表达显著下调。此外,较低的miR-19a-3p表达与肿瘤淋巴结转移分期和淋巴结转移显著相关。此外,分别使用MTT、集落形成、伤口愈合和Transwell Matrigel侵袭试验确定,NSCLC细胞系中miR-19a-3p的上调显著抑制细胞增殖、迁移和侵袭。荧光素酶报告基因检测和蛋白质印迹法确定泛素相关蛋白2样(UBAP2L)是miR-19a-3p的直接靶标,并且在NSCLC中可通过miR-19a-3p的上调而受到抑制。此外,UBAP2L沉默诱导出与miR-19a-3p过表达后观察到的类似效应。UBAP2L的过表达部分逆转了miR-19a-3p对NSCLC细胞系的作用。总体而言,这些数据表明,miR-19a-3p可能部分通过调控NSCLC中UBAP2L的表达而发挥肿瘤抑制作用,并且靶向miR-19a-3p可能是NSCLC治疗的一种新方法。

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