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长链非编码RNA OIP5-AS1通过miR-429/DOCK4调控轴抑制肺腺癌进展并调节巨噬细胞极化。

LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis.

作者信息

Liu Yihan, Wang Yuhua, Cui Long, Li Runze, Xiao Dan

机构信息

Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China.

School of Marxism, Qiqihar Medical University, Qiqihar, China.

出版信息

Front Pharmacol. 2025 May 20;16:1569644. doi: 10.3389/fphar.2025.1569644. eCollection 2025.

Abstract

BACKGROUND

Macrophage polarization plays a pivotal role in shaping the tumor microenvironment and influencing cancer progression. Long non-coding RNAs (lncRNAs) have emerged as important regulators of this process. This study investigated the role of lncRNA OIP5-AS1 in lung adenocarcinoma (LUAD) progression and its involvement in macrophage polarization.

METHODS

The expression of OIP5-AS1 in LUAD tissues and its association with patient prognosis were analyzed. Functional assays, including cell proliferation, migration, invasion, and cell cycle analysis, were conducted in LUAD cell lines. Bioinformatics prediction, luciferase reporter assays, and RNA immunoprecipitation (RIP) were used to explore the interaction among OIP5-AS1, miR-429, and DOCK4. Macrophage polarization and migratory capacity were assessed following manipulation of OIP5-AS1, miR-429, and DOCK4 expression.

RESULTS

OIP5-AS1 expression was significantly decreased in LUAD tissues and associated with poor survival. Overexpression of OIP5-AS1 inhibited LUAD cell proliferation, migration, and invasion, induced G1 phase arrest, and suppressed tumor growth . Mechanistically, OIP5-AS1 functioned as a molecular sponge for miR-429, regulating DOCK4 expression. Overexpression of miR-429 or knockdown of DOCK4 reversed the effects of OIP5-AS1 on macrophage polarization markers and restored macrophage migration.

CONCLUSION

OIP5-AS1 modulates macrophage polarization through the miR-429/DOCK4 axis and inhibits LUAD cell progression. This regulatory pathway may influence the tumor immune microenvironment and represent a potential therapeutic target in LUAD.

摘要

背景

巨噬细胞极化在塑造肿瘤微环境和影响癌症进展中起关键作用。长链非编码RNA(lncRNAs)已成为这一过程的重要调节因子。本研究调查了lncRNA OIP5-AS1在肺腺癌(LUAD)进展中的作用及其与巨噬细胞极化的关系。

方法

分析OIP5-AS1在LUAD组织中的表达及其与患者预后的关系。在LUAD细胞系中进行了包括细胞增殖、迁移、侵袭和细胞周期分析在内的功能实验。采用生物信息学预测、荧光素酶报告基因检测和RNA免疫沉淀(RIP)来探索OIP5-AS1、miR-429和DOCK4之间的相互作用。在调控OIP5-AS1、miR-429和DOCK4表达后,评估巨噬细胞极化和迁移能力。

结果

OIP5-AS1在LUAD组织中的表达显著降低,且与不良生存相关。OIP5-AS1的过表达抑制了LUAD细胞的增殖、迁移和侵袭,诱导G1期阻滞,并抑制肿瘤生长。机制上,OIP5-AS1作为miR-429的分子海绵,调节DOCK4的表达。miR-429的过表达或DOCK4的敲低逆转了OIP5-AS1对巨噬细胞极化标志物的影响,并恢复了巨噬细胞的迁移。

结论

OIP5-AS1通过miR-429/DOCK4轴调节巨噬细胞极化,并抑制LUAD细胞进展。这一调控途径可能影响肿瘤免疫微环境,并代表LUAD的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6477/12171188/16c44ec0092b/fphar-16-1569644-g001.jpg

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