Department of Pathology, Xianyang Central Hospital, Xianyang City, 712000 Shaanxi Province, China.
Crit Rev Eukaryot Gene Expr. 2023;33(2):27-40. doi: 10.1615/CritRevEukaryotGeneExpr.2022044323.
Non-small-cell lung cancer (NSCLC) is the major subtype of lung cancer, with a series of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and proteins involved in its pathogenesis. This study sought to investigate the functionality of lncRNA EPB41L4A antisense RNA 1 (lncRNA EPB41L4A-AS1) in the proliferation of NSCLC cells and provide a novel theoretical reference for NSCLC treatment. Levels of lncRNA EPB41L4A-AS1, miR-105-5p, and GTPase, IMAP family member 6 (GIMAP6) in tissues and cells were measured by RT-qPCR and the correlation between lncRNA EPB41L4A-AS1 and clinicopathological characteristics was analyzed. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. The subcellular localization of lncRNA EPB41L4A-AS1 was analyzed by the subcellular fractionation assay and the binding of miR-105-5p to lncRNA EPB41L4A-AS1 or GIMAP6 was analyzed by dual-luciferase and RNA pull-down assays. Functional rescue experiments were performed to analyze the role of miR-105-5p/GIMAP6 in NSCLC cell proliferation. lncRNA EPB41L4A-AS1 and GIMAP6 were downregulated while miR-105-5p was upregulated in NSCLC tissues and cells. lncRNA EPB41L4A-AS1 was correlated with tumor size and clinical staging and its overexpression reduced NSCLC cell proliferation. lncRNA EPB41L4A-AS1 was negatively correlated with miR-105-5p and positively correlated with GIMAP6 in NSCLC tissues, and lncRNA EPB41L4A-AS1 sponged miR-105-5p to promote GIMAP6 transcription in NSCLC cells. Overexpression of miR-105-5p or knockdown of GIMAP6 reversed the inhibition of lncRNA EPB41L4A-AS1 overexpression on NSCLC cell proliferation. lncRNA EPB41L4A-AS1 was downregulated in NSCLC and mitigated NSCLC cell proliferation through the miR-105-5p/GI-MAP6 axis.
非小细胞肺癌(NSCLC)是肺癌的主要亚型,涉及一系列长链非编码 RNA(lncRNA)、微小 RNA(miRNA)和蛋白质参与其发病机制。本研究旨在探讨 lncRNA EPB41L4A 反义 RNA 1(lncRNA EPB41L4A-AS1)在非小细胞肺癌细胞增殖中的功能,并为 NSCLC 治疗提供新的理论参考。通过 RT-qPCR 测量组织和细胞中 lncRNA EPB41L4A-AS1、miR-105-5p 和 GTPase、IMAP 家族成员 6(GIMAP6)的水平,并分析 lncRNA EPB41L4A-AS1 与临床病理特征之间的相关性。通过细胞计数试剂盒-8 和集落形成实验评估细胞增殖。通过亚细胞分级分析测定 lncRNA EPB41L4A-AS1 的亚细胞定位,并通过双荧光素酶和 RNA 下拉测定分析 miR-105-5p 与 lncRNA EPB41L4A-AS1 或 GIMAP6 的结合。进行功能恢复实验以分析 miR-105-5p/GIMAP6 在 NSCLC 细胞增殖中的作用。在 NSCLC 组织和细胞中,lncRNA EPB41L4A-AS1 和 GIMAP6 下调,而 miR-105-5p 上调。lncRNA EPB41L4A-AS1 与肿瘤大小和临床分期相关,其过表达降低 NSCLC 细胞增殖。lncRNA EPB41L4A-AS1 在 NSCLC 组织中与 miR-105-5p 呈负相关,与 GIMAP6 呈正相关,lncRNA EPB41L4A-AS1 海绵吸附 miR-105-5p 促进 NSCLC 细胞中 GIMAP6 转录。miR-105-5p 的过表达或 GIMAP6 的敲低逆转了 lncRNA EPB41L4A-AS1 过表达对 NSCLC 细胞增殖的抑制作用。lncRNA EPB41L4A-AS1 在 NSCLC 中下调,通过 miR-105-5p/GI-MAP6 轴减轻 NSCLC 细胞增殖。