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miR-301a Deficiency Attenuates the Macrophage Migration and Phagocytosis through YY1/CXCR4 Pathway
Jiawei Xu1,2, Lanya Fu1, Junyao Deng1
1Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, National Demonstration Center for Experimental Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Abstract:
(1) Background: the miR-301a is well known involving the proliferation and migration of tumor cells. However, the role of miR-301a in the migration and phagocytosis of macrophages is still unclear. (2) Methods: sciatic nerve injury, liver injury models, as well as primary macrophage cultures were prepared from the miR-301a knockout (KO) and wild type (WT) mice to assess the macrophage's migration and phagocytosis capabilities. Targetscan database analysis, Western blotting, siRNA transfection, and CXCR4 inhibition or activation were performed to reveal miR301a's potential mechanism. (3) Results: the macrophage's migration and phagocytosis were significantly attenuated by the miR-301a KO both in vivo and in vitro. MiR-301a can target Yin-Yang 1 (YY1), and miR-301a KO resulted in YY1 up-regulation and CXCR4 (YY1's down-stream molecule) down-regulation. siYY1 increased the expression of CXCR4 and enhanced migration and phagocytosis in KO macrophages. Meanwhile, a CXCR4 inhibitor or agonist could attenuate or accelerate, respectively, the macrophage migration and phagocytosis. (4) Conclusions: current findings indicated that miR-301a plays important roles in a macrophage's capabilities of migration and phagocytosis through the YY1/CXCR4 pathway. Hence, miR-301a might be a promising therapeutic candidate for inflammatory diseases by adjusting macrophage bio-functions.
Insights
MicroRNA-301a enhances macrophage migration and phagocytosis by regulating the YY1/CXCR4 pathway. This finding suggests miR-301a as a potential therapeutic target for inflammatory diseases.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- MicroRNA-301a (miR-301a) is implicated in tumor cell proliferation and migration.
- The specific function of miR-301a in macrophage migration and phagocytosis remains largely unknown.
Purpose of the Study:
- To investigate the role of miR-301a in macrophage migration and phagocytosis.
- To elucidate the underlying molecular mechanism of miR-301a in regulating macrophage functions.
Main Methods:
- Utilized miR-301a knockout (KO) and wild-type (WT) mice to establish injury models (sciatic nerve, liver) and primary macrophage cultures.
- Assessed macrophage migration and phagocytosis in vivo and in vitro.
- Employed Targetscan database analysis, Western blotting, siRNA transfection, and CXCR4 modulation to explore the mechanism.
Main Results:
- miR-301a KO significantly reduced macrophage migration and phagocytosis.
- miR-301a targets Yin-Yang 1 (YY1); KO led to YY1 upregulation and downstream CXCR4 downregulation.
- Restoring YY1 expression in KO macrophages enhanced CXCR4 levels, migration, and phagocytosis, while CXCR4 inhibition/activation modulated these functions.
Conclusions:
- miR-301a critically regulates macrophage migration and phagocytosis via the YY1/CXCR4 signaling pathway.
- miR-301a presents a potential therapeutic avenue for inflammatory conditions by modulating macrophage functions.

