MicroRNA regulation of macrophage polarization in lung cancer: Regulatory networks and therapeutic potential (Review)

Abstract

Lung cancer is among the most prevalent and fatal cancers worldwide, with its progression heavily shaped by the tumor microenvironment (TME). As key immune cell populations within the TME of lung cancer, macrophages are involved in the entire process of tumor initiation and development. Macrophage polarization serves as a critical link between inflammation and tumorigenesis and is broadly divided into classically activated M1 and alternatively activated M2 phenotypes. These phenotypes exert tumor-suppressive and tumor-promoting effects, respectively, by secreting distinct cytokine profiles. MicroRNAs (miRNAs/miRs) are a class of endogenous small non-coding RNAs that play broad roles in the malignant progression of lung cancer by regulating various cellular processes, including proliferation, resistance to apoptosis, and metabolic reprogramming. Emerging evidence suggests that miRNAs such as miR-335-5p, miR-106a-5p and miR-99b regulate M1/M2 macrophage polarization by targeting key pathways in lung cancer. Through these regulatory events, miRNAs exert synergistic effects on multiple tumor hallmarks, including proliferation, invasion, migration, apoptosis, angiogenesis, cell cycle progression, stemness maintenance, and epithelial-mesenchymal transition. Collectively, these events drive lung cancer progression and influence therapeutic efficacy. The present review synthesizes recent discoveries to explore the relationship between macrophage polarization and lung cancer, with a specific focus on miRNA-mediated regulatory mechanisms in lung cancer therapy. Ultimately, the present review aimed to provide new insight and a reference point to inform future prevention and treatment strategies for lung cancer.