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

BackgroundMacrophage 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) prog...

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Main Authors: Yihan Liu, Yuhua Wang, Long Cui, Runze Li, Dan Xiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1569644/full
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author Yihan Liu
Yuhua Wang
Long Cui
Runze Li
Dan Xiao
Dan Xiao
author_facet Yihan Liu
Yuhua Wang
Long Cui
Runze Li
Dan Xiao
Dan Xiao
author_sort Yihan Liu
collection DOAJ
description BackgroundMacrophage 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.MethodsThe 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.ResultsOIP5-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 in vitro. 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.
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spelling doaj-art-6c7a9e7a1ef744d4ba2cb37e55fbc9842025-08-20T03:34:31ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15696441569644LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axisYihan Liu0Yuhua Wang1Long Cui2Runze Li3Dan Xiao4Dan Xiao5Graduate School, Heilongjiang University of Chinese Medicine, Harbin, ChinaSchool of Marxism, Qiqihar Medical University, Qiqihar, ChinaDepartment of Oncology, Qiqihar Hospital of Chinese Medicine, Qiqihar, ChinaNational and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin, ChinaNational and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin, ChinaZhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, ChinaBackgroundMacrophage 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.MethodsThe 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.ResultsOIP5-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 in vitro. 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1569644/fullmacrophage polarizationOIP5-AS1miR-429DOCK4lung adenocarcinoma
spellingShingle Yihan Liu
Yuhua Wang
Long Cui
Runze Li
Dan Xiao
Dan Xiao
LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis
Frontiers in Pharmacology
macrophage polarization
OIP5-AS1
miR-429
DOCK4
lung adenocarcinoma
title LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis
title_full LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis
title_fullStr LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis
title_full_unstemmed LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis
title_short LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis
title_sort lncrna oip5 as1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the mir 429 dock4 regulatory axis
topic macrophage polarization
OIP5-AS1
miR-429
DOCK4
lung adenocarcinoma
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1569644/full
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