Wu Xiao-Yan, Xie Yi, Zhou Li-Yun, Zhao Yuan-Yuan, Zhang Jing, Zhang Xiu-Feng, Guo Shuai, Yu Xue-Yan
Shandong Chest Hospital, Department of Respiratory Medicine, Jinan, Shandong, China.
Genet Mol Biol. 2021 May 14;44(2):e20200050. doi: 10.1590/1678-4685-GMB-2020-0050. eCollection 2021.
It has been extensively reported that long noncoding RNAs (lncRNAs) were closely associated with multiple malignancies. The aim of our study was to investigate the effects and mechanism of lncRNA POU6F2-AS1 in lung adenocarcinoma (LADC).The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets provided us the information of LADC clinical samples. High-regulation of POU6F2-AS1 was presented in LADC tissues compared with adjacent normal tissues, which was correlated with poor outcome of LADC patients. Functional experiments in Calu-3 and NCI-H460 cells showed that POU6F2-AS1 significantly promoted LADC cell proliferation, colony formation, invasion and migration. Moreover, through online prediction, luciferase reporter assay and Pearson's correlation analysis, we found that POU6F2-AS1 may act as a competing endogenous RNA (ceRNA) of miR-34c-5p and facilitated the expression of potassium voltage-gated channel subfamily J member 4 (KCNJ4). The promoting effect of cell aggressiveness induced by POU6F2-AS1 was enhanced by KCNJ4, whilst was abrogated due to the overexpression of miR-34c-5p. Collectively, POU6F2-AS1 might function as a ceRNA through sponging miR-34c-5p to high-regulate KCNJ4 in LADC, which indicates that POU6F2-AS1 might be a promising therapeutic target with significant prognostic value for LADC treatment.
已有大量报道表明,长链非编码RNA(lncRNA)与多种恶性肿瘤密切相关。我们研究的目的是探讨lncRNA POU6F2-AS1在肺腺癌(LADC)中的作用及机制。癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据集为我们提供了LADC临床样本的信息。与相邻正常组织相比,LADC组织中POU6F2-AS1呈高表达,这与LADC患者的不良预后相关。在Calu-3和NCI-H460细胞中进行的功能实验表明,POU6F2-AS1显著促进LADC细胞增殖、集落形成、侵袭和迁移。此外,通过在线预测、荧光素酶报告基因检测和Pearson相关性分析,我们发现POU6F2-AS1可能作为miR-34c-5p的竞争性内源性RNA(ceRNA),促进钾离子电压门控通道亚家族J成员4(KCNJ4)的表达。KCNJ4增强了POU6F2-AS1诱导的细胞侵袭性促进作用,而miR-34c-5p的过表达则消除了这种作用。总的来说,POU6F2-AS1可能通过海绵吸附miR-34c-5p作为ceRNA来上调LADC中的KCNJ4,这表明POU6F2-AS1可能是一个有前景的治疗靶点,对LADC治疗具有重要的预后价值。