Department of ICU, Emergency General Hospital, Beijing, China.
Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6767-6778. doi: 10.26355/eurrev_202006_21665.
It is reported that circular RNA plays an important role in various cancers in recent years. However, there is less investigation reported in lung adenocarcinoma (LUAD) about circRNA. This study aims to explore the role and molecular mechanism of circle RNA FOXP1 in LUAD procession.
The levels of circFOXP1 and miR-185-5p in LUAD cell lines and LUAD cancer samples were examined by RT-PCR. The functions of circFOXP1 and miR-185-5p at LUAD cells were detected by cell transfection of the overexpression or repression. The A549 and H1299 cell proliferation were detected by MTT assay and colony formation assay. And the cell apoptosis was detected by TUNEL assay. The expression levels WNT1 were measured by Western blot in A549 and H1299 cells. Furthermore, the luciferase assay detected the direct interaction between circFOXP1 and miR-185-5p or miR-185-5p and WNT1.
The circFOXP1 expression was increased in LUAD patients and LUAD cell lines. The downregulation of circFOXP1 significantly repressed LUAD cell proliferation and promoted cell apoptosis. Moreover, the luciferase assay results confirmed that circFOXP1 directly interacted with miR-185-5p. Overexpression of miR-185-5p could reverse the effect of circFOXP1 in LUAD cell. Besides, the luciferase results showed that miR-185-5p directly interacted with WNT1. miR-185-5p overexpression inhibited the WNT1 expression, while circFOXP1 repression decreased the WNT1 level in LUAD cell lines. The downregulating WNT1 could reverse the effects of miR-185-5p inhibition in LUAD cell lines. Furthermore, WNT1 was significantly upregulated in LUAD cancer tissues. In addition, circFOXP1 level was negatively correlated with miR-185-5p expression and positively correlated with WNT1 expression in LUAD cancer tissues.
These data suggested that circFOXP1 promoted cell proliferation and repressed cell apoptosis in LUAD by regulating miR-185-5p/WNT1 signaling pathway. It provides a novel potential therapeutic agent for the treatment of LUAD.
近年来有报道称环状 RNA 在多种癌症中发挥重要作用。然而，关于肺腺癌（LUAD）中 circRNA 的研究较少。本研究旨在探讨环状 RNA FOXP1 在 LUAD 进展中的作用和分子机制。
通过 RT-PCR 检测 LUAD 细胞系和 LUAD 癌组织中 circFOXP1 和 miR-185-5p 的水平。通过过表达或抑制 circFOXP1 和 miR-185-5p 的细胞转染来检测 circFOXP1 和 miR-185-5p 在 LUAD 细胞中的功能。MTT 检测和集落形成实验检测 A549 和 H1299 细胞的增殖。TUNEL 检测细胞凋亡。Western blot 检测 A549 和 H1299 细胞中 WNT1 的表达水平。此外，通过荧光素酶检测实验检测 circFOXP1 与 miR-185-5p 或 miR-185-5p 与 WNT1 之间的直接相互作用。
在 LUAD 患者和 LUAD 细胞系中，circFOXP1 的表达增加。circFOXP1 的下调显著抑制 LUAD 细胞的增殖并促进细胞凋亡。此外，荧光素酶检测结果证实 circFOXP1 与 miR-185-5p 直接相互作用。miR-185-5p 的过表达可以逆转 circFOXP1 在 LUAD 细胞中的作用。此外，荧光素酶结果表明 miR-185-5p 与 WNT1 直接相互作用。miR-185-5p 的过表达抑制 WNT1 的表达，而在 LUAD 细胞系中抑制 circFOXP1 表达则降低 WNT1 水平。下调 WNT1 可以逆转 miR-185-5p 抑制在 LUAD 细胞系中的作用。此外，在 LUAD 癌组织中，WNT1 表达明显上调。此外，在 LUAD 癌组织中，circFOXP1 水平与 miR-185-5p 的表达呈负相关，与 WNT1 的表达呈正相关。
这些数据表明，circFOXP1 通过调节 miR-185-5p/WNT1 信号通路促进 LUAD 细胞增殖并抑制细胞凋亡。为 LUAD 的治疗提供了一种新的潜在治疗药物。
