Pan Yuejiang, Jin Ke, Xie Xuan, Wang Kexi, Zhang Huizhong
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.
Exp Ther Med. 2020 Sep;20(3):2252-2261. doi: 10.3892/etm.2020.8926. Epub 2020 Jun 24.
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.
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。