ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1569644

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

Provisionally accepted

The final, formatted version of the article will be published soon.

Macrophage polarization plays a pivotal role in shaping the tumor microenvironment and influencing cancer progression, long non-coding RNA (lncRNA) play a crucial role in regulating this process. OIP5-AS1 was shown to influence lung adenocarcinoma (LUAD) progression by modulating macrophage polarization through the miR-429/DOCK4 regulatory axis. OIP5-AS1 expression was decreased in LUAD tissues and correlated with poor survival outcomes. Functional assays demonstrated that overexpression of OIP5-AS1 inhibited LUAD cell proliferation, migration, and invasion, induced G1 phase cell cycle arrest, and suppressed tumor growth in vitro. Bioinformatics analysis, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays confirmed the interactions among OIP5-AS1, miR-429, and DOCK4. Furthermore, overexpression of miR-429 or knockdown of DOCK4 reversed the effects of OIP5-AS1 on macrophage polarization markers and restored macrophage migratory capacity. In conclusion, these findings reveal that OIP5-AS1 acts as a molecular sponge for miR-429, modulating DOCK4 expression and contributing to macrophage polarization. This regulatory axis is involved in shaping the tumor immune microenvironment and may play a role in LUAD progression.

Keywords: Macrophage polarization, OIP5-AS1, miR-429, DOCK4, Lung Adenocarcinoma

Received: 01 Feb 2025; Accepted: 08 Apr 2025.

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