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环状 RNA ABCB10 通过海绵吸附 miR-584-5p 增加 E2F5 表达促进非小细胞肺癌进展。

Circular RNA ABCB10 promotes non-small cell lung cancer progression by increasing E2F5 expression through sponging miR-584-5p.

机构信息

Department of Thoracic Surgery, Peking Union Medical College Hospital , Beijing City, PR. China.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences , Beijing City, PR. China.

出版信息

Cell Cycle. 2020 Jul;19(13):1611-1620. doi: 10.1080/15384101.2020.1761617. Epub 2020 May 18.

Abstract

BACKGROUND/AIMS: CircABCB10 function as an endogenous miRNA sponge plays an important role in various tumors. This experimental design was based on circABCB10 to explore the pathogenesis of non-small cell lung cancer (NSCLC). : CircRNA microarray was used to examine circRNA expression profiles in lung cancer from 3 NSCLC patients and paired healthy lung tissues. The expression of circABCB10 and miR-584-5p was detected by q-PCR. CCK-8, colony formation, and transwell assays to study the circABCB10 effects on tumor cell growth and cell migration invasiveness. To validate downstream target genes of circABCB10 and miR-584-5p detected by luciferase reporter assays. RT-qPCR and Western blotting were used to study E2F5 expression. The tumor growth was detected by nude mice in vivo. : We analyzed the human circRNA expression profile in NSCLC tissues. CircABCB10 was identified as a circRNA that increased in NSCLC tissues. CircABCB10 was noticeably raised in NSCLC, and high circABCB10 expression was related to low survival in NSCLC patients. Silencing of circABCB10 suppressed non-small cell lung cancer cell migration, cell proliferation, and invasion.CircABCB10 can act as a sponge of miR-584-5p to up-regulate E2F5 expression level. E2F5 knockdown or overexpress of miR-584-5p gene reversed the circABCB10 who has carcinogenic effects. There was a negative correlation expression between the circABCB10 and miR-584-5p gene, and There was a positive relationship between the expression of circABCB10 and E2F5 in NSCLC tumors. : CircABCB10 promoted the progression of NSCLC by modulating the miR-584-5p/E2F5 axis.

ABBREVIATION

NSCLC: non-small cell lung cancer; circ RNA: circular RNA; miRNA: micro RNA.

摘要

背景/目的:CircABCB10 作为内源性 miRNA 海绵的功能在各种肿瘤中发挥重要作用。本实验设计基于 circABCB10 来探讨非小细胞肺癌(NSCLC)的发病机制。方法:使用 circRNA 微阵列检测 3 例 NSCLC 患者和配对的健康肺组织中的肺癌 circRNA 表达谱。通过 q-PCR 检测 circABCB10 和 miR-584-5p 的表达。通过 CCK-8、集落形成和 Transwell 测定研究 circABCB10 对肿瘤细胞生长和细胞迁移侵袭的影响。通过荧光素酶报告测定验证 circABCB10 和 miR-584-5p 的下游靶基因。使用 RT-qPCR 和 Western blot 检测 E2F5 的表达。通过体内裸鼠检测肿瘤生长。结果:我们分析了 NSCLC 组织中的人类 circRNA 表达谱。鉴定出 circABCB10 是 NSCLC 组织中上调的 circRNA。CircABCB10 在 NSCLC 中明显升高,并且 NSCLC 患者中高 circABCB10 表达与低生存率相关。沉默 circABCB10 可抑制非小细胞肺癌细胞迁移、细胞增殖和侵袭。CircABCB10 可作为 miR-584-5p 的海绵,上调 E2F5 表达水平。E2F5 敲低或 miR-584-5p 基因过表达逆转了 circABCB10 的致癌作用。CircABCB10 基因与 miR-584-5p 基因之间呈负相关表达,而在 NSCLC 肿瘤中 circABCB10 与 E2F5 的表达呈正相关。结论:CircABCB10 通过调节 miR-584-5p/E2F5 轴促进 NSCLC 的进展。缩写:NSCLC:非小细胞肺癌;circRNA:环状 RNA;miRNA:微小 RNA。

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