ABSTRACT

Lung adenocarcinoma (LUAD) is a deadly cancer with a high incidence worldwide. Long noncoding RNAs (lncRNAs) have been confirmed to have the regulatory effects on the occurrence and development of LUAD. But the specific functions of lncRNA GLIDR in LUAD are still not explicit and need to be investigated. On the basis of the outcomes of RT-qPCR experiments, the relative expression of GLIDR was evidently up-regulated in LUAD cells, while that of miR-1270 was down-regulated. The down-regulation of GLIDR inhibits cell proliferation in accordance with the results of CCK-8, EdU and colony formation assays, and accelerates cell apoptosis according to the results of flow cytometry and JC-1 analyses. Luciferase reporter, RNA pull down and RIP assays indicated that GLIDR could sponge miR-1270 in LUAD. Additionally, TCF12 was proved as the target gene of miR-1270. Furthermore, rescue experiments indicated that overexpression of TCF12 could offset the inhibitory functions of silencing GLIDR on cell behaviors. In brief, this study has demonstrated that GLIDR/miR-1270/TCF12 axis plays the crucial role in LUAD, which offers a new insight into researches on molecular mechanism concerning LUAD and provides with a new perspective for LUAD treatment.

摘要

肺腺癌 (LUAD) 是一种致命的癌症，在全球范围内发病率很高。长链非编码RNA（lncRNA）已被证实对LUAD的发生和发展具有调节作用。但lncRNA GLIDR在LUAD中的具体功能尚不明确，需要进一步研究。根据 RT-qPCR 实验结果，LUAD 细胞中 GLIDR 的相对表达明显上调，而 miR-1270 的相对表达下调。根据 CCK-8、EdU 和集落形成测定的结果，GLIDR 的下调抑制细胞增殖，并根据流式细胞术和 JC-1 分析的结果加速细胞凋亡。荧光素酶报告基因、RNA pull down 和 RIP 分析表明 GLIDR 可以海绵 LUAD 中的 miR-1270。此外，TCF12被证明是miR-1270的靶基因。此外，救援实验表明，TCF12 的过表达可以抵消沉默 GLIDR 对细胞行为的抑制作用。总之，本研究表明GLIDR/miR-1270/TCF12轴在LUAD中起关键作用，为LUAD的分子机制研究提供了新的视角，为LUAD的治疗提供了新的视角。