Related Experiment Video For Circular RNA
Updated: Jun 14, 2026
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
circHIF1A/miR-486-5p/GRHL2 axis induces macrophage M2 polarization to accelerate lung adenocarcinoma progression
Guanying Zheng1, Yizhen Chen2, Yuxin Wang2
1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, China; Department of Respiratory Medicine and Critical Care Medicine, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
Background:
The mechanisms underlying the early progression of lung adenocarcinoma (LUAD) remain unclear, and the interaction between circular RNAs (circRNAs) and the immune microenvironment lacks systematic investigation. While circHIF1A has been reported to possess oncogenic functions in colorectal and breast cancers, its specific role in LUAD and whether it regulates the tumor microenvironment via a competing endogenous RNA (ceRNA) mechanism remain to be elucidated.
Methods:
Tumor and paired paratumorous normal tissues were collected from 80 LUAD patients. Using A549 and H1299 cell lines and the nude mouse subcutaneous xenograft model, we systematically analyzed the expression characteristics, biological functions, and molecular mechanisms of circHIF1A.
Results:
circHIF1A was significantly upregulated in LUAD, and its expression level was positively correlated with advanced TNM stage and poor patient prognosis. Mechanistically, circHIF1A functions as the ceRNA to specifically sponge miR-486-5p, thereby relieving the transcriptional repression of its downstream target gene, GRHL2, forming the circHIF1A/miR-486-5p/GRHL2 regulatory axis. This axis not only directly enhances LUAD cell proliferation, stemness maintenance, migration, and invasion but also induces macrophage M2 polarization by promoting IL-10 secretion, thereby establishing an immunosuppressive microenvironment. In vivo experiments confirmed that intervening in the circHIF1A/miR-486-5p/GRHL2 axis significantly inhibits LUAD tumor growth.
Conclusion:
circHIF1A regulates malignant phenotypes of LUAD cells and tumor microenvironment remodeling through a ceRNA network. The mediated circHIF1A/miR-486-5p/GRHL2 axis provides a novel molecular biomarker for LUAD prognostic assessment and represents a potential target for therapeutic intervention.
